Document RjB6bB4p54wMLyrqZm7wMwKVE

vinyl chloride: An Information Resource prevention Branch Division of Cancer Control and Rehabilitation Thomas H. Milby, M.D. Editor National Cancer Institute Bethesda. Maryland u.s. Department of Health, Education, and Welfare Public Health Service National Institutes of Health m DHEW Publication Number (NIH) 78-1599 March 1978 21910001 BFG17016 ;r CONTENTS LIST OF ILLUSTRATIONS.................................................................................................... vli LIST OF TABLES......................................................................... ix Chapter I--INTRODUCTION AND REGULATORY HISTORY .... ........................... 1 Early Evidence of Problems ...................................................................... 1 Acroosteolysls ................................................................................................ 1 ' Li\ ~r Cancer c>m'A Development of Stringent Regulatory Controls ................................................................. .... 2 Beverages, Foods, and Other Consumer Products . .'.................. The General Environment ............................................................. ... 2 3 Transportation of Vinyl Chloride ................................... ..... 4 Extent of Potential for Exposure.................................. 4 Chapter II--PRODUCTION, USE, EMISSIONS, AND HUMAN EXPOSURE ..... 7 Production and Consumption ...................................................................... 7 Production Processes ................................... .... ........................... 9 Vinyl Chloride.............................. Polyvinyl Chloride Resins ...................... . ............................... Compounding of PVC Resins .............................................................. Conversion to End Products.................................m............................. Emissions and Their Sources............................................................. . 9 16 17 18 18 Polymerization of Vinyl Chloride to FVC ............................... Production of Vinyl Chloride Monomer ........................................ Fabrication of PVC Products.......................... General Environment and Miscellaneous Sources .................. 18 20 21 22 111 BFG17017 219100Q2 C) Dispersion end Degradation of Vinyl Chloride . ................................ 24 Atmosphere.............................. 25 Uater and Soil........................................................................................26 Source/Exposure Model 27 Chapter III--NONCARCINOGENIC EFFECTS OF VINYL CHLORIDE ................................ 31 Animals, Microorganisms, and Plants ..................................................... 31 Toxicity to Humans........................................................................................ 33 Acute Intoxication.....................................................................................33 Disturbances in Liver Function ..................................................... 34 Acroosteolysis ........................................................................................ 35 Changes in the Lung............................................................................... 35 Hematologic Changes ........................................ .................................... 36 Chromosomal Aberrations, Excess Fetal Death Ra^e, and Birth Defects......................................................... -.........................36 Chapter IV--CARCINOGENICITY OF VINYL CHLORIDE.................................................39 Animal Studies ................................................................................................. 39 Mice....................................................................................................................39 Rats..................................................................................................... 42 Hamsters....................................................................................... 42 Epidemiology and Case Report;............................................... 45 Case Reports . . . ..................................................................................... 45 Cohort Studies ......................................................................................... 47 Community Studies .................................................................................... 53 Dose-Response Relationships .............................................................. 53 Discussion.......................................................................................................54 Chapter V--CANCER CONTROL PROGRAM FOR EXPOSURE TO VINYL CHLORIDE ... 57 Engineering Control ......................................................................................... 57 Monitoring for Vinyl Chloride Exposure ... ....................... Control Measures for Emission Sources Personal Protective Measures . . ................................................. Additional Sources of Information ................................................. 57 64 68 68 21910003 :r Medical Surveillance ....................................................................................... 68 Overview.........................................................................................................70 OSHA Requirements......................................................................... 70 A Medical Surveillance Program--Louisville, Ky...................... 71 Educational Control ..................... 72 OSHA Regulations--Education.................................................................. 73 Understanding "Risk" ... ............................................................. 73 A National Academy of Sciences Study ........................................ 74 Implications and On-going .Programs........................................... 79 CHAPTER VI--A VINYL CHLORIDE CONTROL PROGRAM FOR A TOWN OF 25,000-- A SCENARIO........................................................................................................ 83 The County Medical Society ............................................................. 84 County Health Department ................................................................. 85 Plant Management....................................................................................... 90 The Plant Union ............................................................................................91 American Cancer Society ...................................................................... 92 APPENDICES ^ A--Vinyl Chloride-Related Compounds 53 B--One PVC Producer's Approach to Evaluation and Control' of Vinyl Chloride Exposure ................................................ 97 C--Sources for Further Information ............................................................. 105 D--References................................................................................................................ Ill 21910004 BFG17019 ( LIST OF ILLUSTRATIONS 1 Regulation of Vinyl Chloride as a Health Hazard in the U.S.................. 6 2 Locations of Vinyl Chloride and Polyvinyl Chloride Plants in the 'United States.......................... .... .......................................... . . . IS 3 Production and Use of Vinyl Chloride............................................................. 19 4 Environmental Flow of Vinyl Chloride to Man...................... ......................... 29 5 Simplified "Typical" Process for Production of Vinyl Chloride Monomer (VCM) ...... ........................................................ ...................... 58 6 Simplified "Typical" Polymerization Process ................................................ 59 7 Simplified "Typical" Fabrication Operation ................................... . 60 8 National Cancer Institute, Comprehensive Cancer Centers ...... 86 I 21910005 vii BFG17020 n ( LIST OF TABLES 1 Physical Properties of Vinyl Chloride .......................................................... 5 2 Production, Exports, and Apparent Consumption of Vinyl Chloride, United States, 1970-1974 . . ............................................................................... 8 3 U.S. Producers of Vinyl Chloride ................................................................... 10 4 U.S. Producers of Polyvinyl Chloride ........................... .... 12 5 Range of Vinyl Chloride Concentrations in Some Categories of Consumer Products ............................................................................................... 25 6 Estimated Environmental Persistance of Vinyl Chloride ....................... 28 7 Relative Importance of Vinyl Chloride Exposure for a "Standard Man".............................................................................................. 30 8 Incidence of Tumors in Mice Exposed to Vinyl Chloride for 30 Weeks and Dying Within 34 Weeks............................................................... 40 9` I .cidance ot T'T'ors in Mice Exposed tc Vinyl Chloride for 37 Weeks ?nd c'ir''Lvi.i up to 41 Meeks.......................................................... 41 10 Incidence of Tumors in Rats Exposed to Vinyl Chloride for 52 Weeks and Surviving up to 130 Weeks......................................................43 11 Incidence of Tumors in Hamsters Exposed to Vinyl Chloride for 28 Weeks......................................................................................................................44 12 Summary TaDle of Cohort of Occupational Exposure to Vinyl Chloride.............................................................................................................48 13 Advantages and Disadvantages ofMajor Monitoring Strategies ... 63 14 Possible PVC Substitutes........................................................................................... 69 15 What the Employee and Employer Should Know About Occupational Cancer in General............................................................................................................. 76 16 What the Employee and Employer Should Know About A Specific Carcinogenic Substance........................................................ 77 17 National Cancer InformationService ............................................................. 87 21910006 BFG17021 ;i ACKNOWLEDGMENTS SRI International, Center for Occupational and Environmental Safety and Health, acknowledges the invaluable advice and assistance of the fol lowing individuals during the preparation of this monograph on vinyl chloride: David B. Clayson, Ph.D., Assistant Director Eppley Institute for Research in Cancer Joseph W. Cullen, Ph.D., Deputy Director UCLA Cancer Center, University of California at Los Angeles Ian T. T. Higgins, M.D., Professor School of Public Health, The University of Michigan Morton S. Hilbert, M.P.H., Professor School of Public Health, The University of Michigan Phillipe Shubik, M.D., Director Eppley .Institute for Research in Cancer James Whittenberger, M.D., Chairman Department of Physiology, Harvard School of Public Health Harvard University BFGI7022 21810007 Chapter I INTRODUCTION AND REGULATORY HISTORY Vinyl chloride monomer is a widely used chemical, the parent compound of polyvinyl chloride (PVC), a plastic resin used in innumerable consumer and industrial products--containers, wrapping film, electrical insulation, pipelines, credit cards, and many other items. At the same time, however, it can be said that overwhelming scientific evidence shows vinyl chloride to be a human carcinogen. Moreover, medical evidence suggests a strong as sociation between exposure to vinyl chloride and the occurrence of a num ber of toxic, nonmalignant illnesses involving skin, bones, liver, lungs, and blood. PVC and other vinyl chloride polymers are not, at the time of this writing, considered to represent a carcinogenic risk to man. Early Evidence of Problems First produced commercially in the United States in 1927, vinyl chlo ride gas was for many years regarded by toxicologists as having only mod erate liver toxicity. It was once considered for use as a general anes thetic, but its use for this purpose was abandoned in the early 1930s after experiments in animals demonstrated that its anesthetic effects were often accompanied by cardiac irregularities. In 1961, a threshold limit value (TLV) of 500 parts per million (ppm) for vinyl chloride was suggested by the American Conference of Governmental Industrial Hygien ists (ACGIH), a standard apparently based upon its narcotic properties. Acroosteolysis In 1967, a hitherto unrecognized occupational disease was reported to be associated with exposure to vinyl chloride. This disease appeared among workers engaged in the process by which vinyl chloride was reacted (polymerized) to PVC. The disease was termed occupational acroosteolysis (AOL). Its symptoms included tenderness of the fingertips, sometimes ac companied by a gradual destruction of the bony integrity of the fingers. Workers suffering from this condition exhibited a. form of vascular disease known as Raynaud's phenomenon. Only workers involved in the manual clean ing of PVC reactor vessels developed AOL. \ In 1972, the ACGIH lowered Its TLV for vinyl chloride to 200 ppm, following appearance of the evidence linking exposure to vinyl chloride with development of AOL, as well as new evidence of liver dysfunction among vinyl chloride workers. 8000T6T2 1 Liver Cancer and Development of Stringent Regulatory Controls Then, on January 22, 1974, Che Occupational Safety and Health Admin istration (OSHA) was informed by the National Institute for Occupational Safety and Health (NIOSH) that the fi. F. Goodrich Chemical Company had reported the deaths of several employees from a rare liver cancer (angio sarcoma >. -Shortly thereafter, a fact-finding hearing was held by the U.S. Department of Labor. As a result, on April 5, 1974, the Department of Labor promulgated an emergency temporary exposure standard. This standard reduced the per missible exposure level to 50 ppm and established other safety require ments. On May 10, OSHA proposed a permanent standard consisting of a downward revision of the temporary standard to a "nondetectable level," as measured by a sampling and analytical method sensitive to 1 ppm. This proposed standard also contained occupational health requirements in ad dition to limitations on airborne levels. A hearing on the proposed permanent standard was conducted in late June and early July of 1974, and a permanent standard was established. This standard set an exposure limit of 1 ppm averaged over any 8-hour period, with a ceiling of 5 ppm averaged over any period not exceeding 15 minutes. Health and safety requirements, including medical surveil lance, were also established. In addition, the standard provided for an "action level" of 0.5 ppm time-weighted average. When monitoring demonstrates that no employee is exposed in excess of this action level, the employer may be exempted from some provisions of the standard. The purpose of this action level is to minimize the impact of the standard on employers who have attained exposure levels well below the permissible 1imit. Beverages. Foods, and Other Consumer Products Meanwhile, other concerns over the potential adverse effects of vinyl chloride had been voiced. In 1973, it was discovered by the Food and Drug Administration (FDA) that vinyl chloride could migrate from PVC containers into alcoholic beverages stored in them. Accordingly, the use of PVC bottles to contain distilled spirits was prohibited by the U.S. Treasury Department. Discovery that vinyl chloride could also migrate from PVC containers to nonalcoholic beverages and to foods eventually led the FDA to propose, in September of 1975, more general regulations regarding vinyl chloride polymers in contact with food. At the time of this writing, the proposed FDA regulations state that any food containing detectable levels of vinyl chloride would be deemed adulterated. Hence, all uses of vinyl chloride polymers in rigid and semi-rigid food contact materials, such as bottles and sheets, would be prohibited because, in those forms, entrapped vinyl chloride may reasonably be expected to become a component of the food. The proposal would permit, however, the continued use of the "film" type of vinyl chloride polymers in food packaging and in other food contact 2 BFG17024 1 6000T6TZ / materials such as bottle cap linings, can coatings, and gaskets, since in these forms the migration of vinyl chloride is reduced to extremely low levels. The proposal includes an interim food additive regulation allowing the use of water pipe made from vinyl chloride polymers. This interim regulation would remain in effect pending development of additional data to determine if vinyl chloride may be reasonably expected to exist in potable water that is drawn from systems using such water pipe. Prelim inary data from an Environmental Protection Agency (EPA) survey of com munity drinking water supplies indicate that, although vinyl chloride can occasionally be found in small concentrations, the actual source of it is yet unknown.* The use of vinyl chloride as a propellant in aerosol cans designated for household use was banned in 1974 through separate actions of the FDA, EPA, and Consumer Product Safety Commission (CPSC). A recall order on aerosol cans containing vinyl chloride was finalized in September of 1975 by the CPSC. In order to protect consumers from the possible migration of vinyl chloride from PVC articles, the FDA is, at the time of this writing, work ing on proposals to regulate the use of PVC as a container for drugs and cosmetics, and in medical devices. Although these proposals will likely be patterned a.f!-;-.': the FDA's proposed regulations .-n food contact raaterials, they must necessarily utilize slightly different approaches because of the difference in the agency's statutory authority over these areas. The General Environment On October 21, 1976, the Environmental Protection Administration (EPA) promulgated regulations requiring the installation of the best available control technology to reduce vinyl chloride emissions to the air from all point and fugitive emission sources in plants that manufac ture ethylene rfichlonde (by the oxychlorination process), vinyl chloride, or PVC. In addition, vinyl chloride emissions are limited to 0.02 g/kg of ethylene dichloride product. These regulations apply to all exist ing and new ethylene dichloride plants, vinyl chloride plants, and PVC plants in the U.S. The EPA estimates that these regulations will result in reduction of vinyl chloride emissions to the ambient air from hitherto uncontrolled sources by more than 90Z. These regulations resulted in part from an EPA study of ambient concentrations of vinyl chloride in residential areas located in the vicinity of vinyl chloride or PVC plants. This study showed that although the ambient levels of vinyl chloride exceeded 1 ppm less than 10Z of the time, the new regulations 0T00TGT2 *The question of whether this issue falls within the jurisdiction of the FDA or the EPA is being debated by the two agencies at the time of this writing. 3 bGV>025 :r could have a significant impact on the total vinyl chloride exposure of the approximately 4.6 million people living within a 5-mile radius of these plants. Although the disposal of vinyl chloride into ocean waters has been banned, there are currently no regulations on vinyl chloride emissions into other water systems. However, the EPA air emissions standard indi rectly affects water emissions, since it establishes a 10 ppm limitation on in-process waste water. This restriction, in conjunction with the ten dency of vinyl chloride to escape from water, makes significant waterpollution problems unlikely. The disposal of solid waste containing vinyl chloride is not cur rently seen as being a major cause for concern. The EPA, howver, is draw ing up guidelines that would ensure the safe disposal of such waste. Transportation of Vinyl Chloride Although some vinyl chloride is transported by barge arid truck, most of it is shipped by rail tank car. In a three-year period from 1971-1974, there were 16 reported rail accidents involving vinyl chloride tank cars. The Department of Transportation (DOT) has regulatory responsibility over the transportation and handling of vinyl chloride as a "hazardous material." Regulations by DOT include requirements for transportation preparations such as construction of containers, packaging, volume, and marking. Until recently, DOT. regulations were directed almost exclusively to the fire and explosion hazard of this very flammable gas. In April 1975, however, the Coast Guard (a branch of DOT) promulgated new regula tions for thf* --*nsport of vinyl chloride by barge. These regulations would require the implementation of control measures similar to those specified in the OSHA regulations. Extent of Potential for Exposure As indicated previously, the potential for human contact with vinyl cnloriae is great. There is, first of all, production of the compound itself (vinyl chloride monomer); in the United States, some 2.5 billion kilograms (5.6 billion pounds) per year are produced at 15 plants employ ing some 900 workers. Also, vinyl chloride is polymerized to produce PVC at 39 plants employing over 5,500 workers, and tens of. thousands of workers fabricate PVC into the many products that reach consumer and in dustrial users. Finally, EPA has estimated that nearly 5 million people reside sufficiently close to the nation's vinyl chloride facilities to be within range of detectable airborne concentrations of the gas. In the chapters that follow, the production, uses, and dispersion of this hazardous compound are discussed, evidence of its toxic and car cinogenic effects is summarized, and control strategies and programs are set forth. 4 21910011 BFG17026 ir Table 1 PHYSICAL PROPERTIES OF VINYL CHLORIDE* Formula ..... .............................................................................. CH2:CHC1 Molecular weight ............................................................................... 62.50 Melting point ....................................................................................... -153.7 Boiling point, 1 atm ...................................................................... -13.9*C (7.0*F) Specific gravity, gat, 15*C, 1atm (air >1)......................2.15 flash point ...................................................................... ..... -78*C (-108*F) Self-ignition temperature ............................................................. 472*C (881.6*F) Explosive limits in air, 2by vol.............................................. 4-20 Viscosity, liquid, eP -40"C..................................................................................................... -?0*C.................................................................................................... -20#C.......................... .... ..................................................... -10C.................................................................................................... 0.3339 0.3026 0.2780 0.2563 Vapor pressure C atm atm -30 0.50 -20 0.77 -10 1.17 0 1.70 10 2.43 Solubility in water . 24*C. 1 atm 20 3.33 30 4.51 40 5.94 50 7.80 60 9.93 ..... Conversion factors, 25*C, 1 atm 1 ppm . . 1 mg/liter . . . ^Compiled from: Kirk-Othmer Encyclopedia of Chemical* Technology, Second edition, Vol. 5 (Interscience Publishers, John fclilcy 6 Sons, Inc., New York, 1964), p. 172; and from U.S. Environmental Protection Agency, Of fice of Research and Development, "Scientific and Technical Assessment Report on Vinyl Chloride and Polyvinyl Chloride," Report No. EPA-600/675-004 (Washington, D.C., U.S. Govt. Printing Office, 1975), p. 6. 5 ZT00T6TZ BFG17027 ------------iwi--------- ------------ raj---------- -----------im---------- -----------raj--------- ------------raj--------- ------------ rai---------- ----------- TTT5---------- ----------- rm----------- AMticw CMftnm af ftwinutil Xw' ^risl Bjiiw- liMblUM tkraakmlf limit llM (TLT) af SOO Pfm Miiiu see n nv tfin limit tm SOO avm ulaa tMtntratiaa laaiaae SOO asm --tmum tarnaa- tratiaa limit tanari ta roe rra -w-i CuH (Deaartaoot tf TreatMrut&ai) --r Mud Safety CtauitiM tafirtemial Promtiot Agency State t tka aaa af tiayl ckla* riaa aa a prapallaat U aaraaala OamaaS the aaa af aiapl aklaria aa a prpc 11amt ia aaraaala fraaaliataf aaa rapvlatiaaa far traaepartatiaa iarl cklariOa kp katp (aaaaaraa aiallar ta Otat rapala- *`~>t rUaliaaf (U Sept.) a recall aa aaraaal caaa caataiaiap ai apl tkleriOe (Doc )--proponed rogoletiona reftiriti ioetallotion of boat available techoology to rodoce eoiasiees to air and a 10 ppo Unit for inprocess vests veter. Feed and Maiaiiiritiot laaaaf tba of vinyl chlo ride propellant in aoroaola Proposed roguletiona prohib iting any de tectable level in food, there by prohibiting one of rigid and teoi-rigid vinyl chloride polyners as food containers Working on pro posals to rege late ese of PVC as container material for drugs, cosmet ics. and nodical devices SectMtiMil Safttjr end Naattl Mtiaii- r^r Published list of TLV*a for paHataati ia tli* verb alaea-- vinyl chloride Unit it at 500 PP April 5--Sat Emergency To*- porary Standard at 50 ppo; Oct. 1--50 ppo m4o permanent through Ore. 31 than dropped to 1 ppo over t-hr period and 5 ppo for 15-aine pe riods Traaavry Dopartnoat Prohibited aaa of PVC bottlta to contain dis tilled spirits Advisory only. Department of Transportation refutations have required all along that vinyl chloride be transported and handled as a "hazardous material." ET00T6T2 \ ( FIGURE 1 REGULATION OF VINYL CHLORIDE AS A HEALTH HAZARD IN THE U.S. 6 BFG17028 Chapter II PRODUCTION, USE, EMISSIONS, AND HUMAN EXPOSURE A major part of any carcinogen control program is quite direct in concept--reducing human exposure to a carcinogenic agent. Effective reduc tion of exposure, in turn, depends upon understanding at what points in the exposure pathways control measures can be implemented successfully. In par ticular, it is important to understand which sources of exposure are domi nating, so that limited control resources can be applied most judiciously. Exposures to vinyl chloride occur in the workplace, through general air and water pollution, and, to a limited extent, from the use of fab ricated products. Although large quantities of vinyl chloride are pro duced each year in the United States, it is not in the production of the chemical itself that the greatest potential for harmful exposure exists. Rather, the greatest hazard is when the chemical is polymerized to form other materials, nearly all of which are polyvinyl chloride (PVC) resins, during which process vinyl chloride escapes into the air. Inhalation of this vinyl chloride is by far the most important exposure pathway. This chapter examines the production and use of vinyl chloride in the United States and emissions of the chemical into the environment, all of which are factors in human exposure. From this information, a conceptual model, which will be found at the end of this chapter, has been made to illustrate the flow of vinyl chloride from its sources to the populations at risk. Production and Consumption**^ Some 2.5 billion kilograms (kg) of vinyl chloride are produced in the United States each year. About 188 million kg of the material were exported in 1975; imports of vinyl chloride are negligible. (See Table 2.) Virtually all (96Z) of the more than 2 billion kg consumed in the United States are for production of PVC (2.2 billion kg in 1974, 1.7 billion in 1975, and an estimated 2.2 billion in 1976). After being compounded with various other materials, PVC is converted to a variety of end products. Categories of end use for PVC products and the estimated proportion of total production for each are (1975): Construction (primarily pipe and conduit) Consumer goods Electrical Packaging 48Z 16 8.5 8.5 7 21910014 BFG17029 Transportation 6 Home furnishings 6 Miscellaneous 7 ( (coatings, adhesives, and inks; medical tubing and bloodbags; credit cards, carpet back- coatings; traffic cones; novelties, etc.) The 4Z of vinyl chloride not used in producing PVC is used for the most part to produce methyl chloroform, which is used primarily as a sol vent. Vinyl chloride was once used in the production of Dynel* acrylic fibers, but that production was discontinued in 1974. As noted in the previous chapter, use of vinyl chloride as a propellant in aerosol cans was banned in 1974. It has been reported that vinyl chloride has found use in the production of chloroacetaldehyde, an intermediate in the synthe sis of sulfa drugs, but no evidence was found in this study that it is currently being used for this purpose. Also, it has been reported that vinyl chloride found use as a refrigerant and as an extraction solvent for heat-sensitive materials; however, no evidence was found that it is currently being used for these purposes. Table 2 PRODUCTION, EXPORTS, AND APPARENT CONSUMPTION OF VINYL CHLORIDE, UNITED STATES, 1970-1975* (Millions of kg) Apparent U.S. Year Product ion Exports Consumption 1970 1971 1972 1973 1974 1975 1976 1834.2 1968.5 2310.4 2429.4 2551.9 1905.0b 2604.QC 302 281 282 191 187 188 1532 1688 2028 2238 2365 1717 ^Imports are negligible. Pales value of the vinyl chloride pro duced in 1975 was roughly $438 million (based on a price of 25c/kg, tank quan tities, polymer grade, FOB works, also applied to material used in captive con sumption). Preliminary estimate. Source: SRI 8 21910015 BFG17030 Long-term demand for FVC in its major markets is expected to remain stable, since its uses are firmly established and because there is no ma terial that can readily replace it. Although investigations by the Envi ronmental Protection Agency and industry of any possible leaching of vinyl chloride into drinking water are continuing, it does not appear now that the continued growth of PVC consumption for water supply pipe will be cut off by any regulatory action, especially since pipe resins are now made with controlled, negligibly low, levels of residual vinyl chloride monomer. And although there is public concern over migration of vinyl chloride from PVC packaging film and bottles into the containers' contents, and the makers of cosmetics and toiletries are abandoning the use of PVC bottles, loss of volume in the packaging industry affects only a minor part of the market for PVC.2 it is estimated that consumption of PVC in 1980 will be about 3 billion kg. Ten U.S. companies manufacture vinyl chloride at 15 plants in the nation, including Puerto Rico. (See Table 3.) There are 22 producers of PVC resins at 39 plants in the country. (See Table 4; plant locations, for vinyl chloride as well, are also shown in Figure 2.) Allied Chemical Corporation, Dow Chemical U.S.A., PPG Industries, Inc., and Shell Chemical Company only produce vinyl chloride for sale to others; the other companies also produce PVC resins. Most large manufacturers of resin also produce PVC resin compounds for sale or for toedinp their own end-product menvfr- For exaiuple, Continental Oil Company, Conoco Chemical* Division, has n FVC compound production capacity of over 60 million kg per year at Aberdeen, Mississippi, and the Plastics Division of Diamond Shamrock Chemical Company has two com pounding plants with a combined capacity of nearly 80 million kg per year. The B. F. Goodrich Chemical Company has long operated several large compounding facilities. Other resin manufacturers that compound resins are Robintech, Inc., Ethyl Corporation, Pantasote Company, Tenneco Chemicals, Inc., and Firestone Plastics Company. Resins are also compounded by an estimated two dozen other firms in the United States, the largest of which is believed to be H. Schulman, Inc., Akron, Ohio. Production Processes^ The processes for manufacturing both vinyl chloride and its polymers, polyvinyl chloride resins, are described briefly in the paragraphs that follow. 21910016 Vinyl Chloride Nearly all of the vinyl chloride produced commercially in the United States is currently made from ethylene by one or the other of two processes (abet half by each): oxychlorination of ethylene and direct chlorination of ethylene. A third process, addition of hydrogen chloride to acetylene, accounts for about 4Z of the total vinyl chloride produced. 9 BFG17031 Table 3 U.S. PRODUCERS OF VINYL CHLORIDE Company and Plant Location Shell Oil Company, Shell Chemical Company, Base Chemicals Division Deer Park, Texas Norco, Louisiana Dow Chemical U.S.A. Oyster Creek, Texas Plaquemine, Louisiana Freeport, Texas The B. F. Goodrich Company, B. F. Goodrich Chemical Company Division Calvert City, Kentucky PPG Industries, Inc. PPG Industries (Caribe), Guayanilla, PR Industrial Chemicals Division Lake Charles, Louisiana Continental Oil Company, Conoco Chemicals Lake Charles, Louisiana Ethyl Corporation, Industrial Chemicals Division Baton Rouge, Louisiana Pasadena, Texas Allied Chemical Corporation, Industrial Chemicals Division Baton Rouge, Louisiana Borden Inc., Borden Chemical Division, Petrochemicals Geismar, Louisiana Annual Nameplate8 Production Capacity Year End, 1976 (million kg) Plant | Total 700 380 320 610 320 200 90 450 410 230 180 320 180 120 60 140 140 10 21910017 BFG17032 Table 3 (Concluded) Monochem, Inc. (jointly owned by Borden, Inc. and Uniroyal, Inc.) Geismar, Louisiana Stauffer Chemical Company Carson, California Total Annual Nameplate* Production Capacity Year End, 1976 (million kg) Plant | Total" 140 80 _____ 3170 \ 21910018 aActual operating capacities are usually somewhat lower. Published capaci ties are often larger because (1) design capacities presume the continuous production of one type of resin whereas all producers make various types of resins in each plant, and (2) scheduled and unscheduled shutdowns are not taken into account in nameplate capacity figures. Source: SRI 11 BFG17033 Table 4 U.S. PRODUCERS OF POLYVINYL CHLORIDE Company and Plant Location The B. F. Goodrich Company, B. F. Goodrich Chemical Company Division Louisville, Kentucky Pedricktown, New Jersey Avon Lake, Ohio Henry, Illinois Long Beach, California Diamond Shamrock Corporation, Diamond Shamrock Chemical Company, Subsidiary, Plastics Division Deer Park, Texas Delaware City, Delaware Borden, Inc., Borden Chemical Division Illiopolis, Illinois Leominster, Massachusetts Tennero Inc.. Tenneco Chemicals, Inc. Organics and Polymers Division Pasadena, Texas Burlington, New Jersey Flemington, New Jersey Tne Firestone Tire & Rubber Company, Firestone Plastics Company, Division Pottstown, Pennsylvania Perryville, Maryland Stauffer Chemical Company, Plastics Division Delaware City, Delaware Long Beach, California Continental Oil Company, Conoco Chemicals Division Oklahoma City, Oklahoma Aberdeen, Missouri 12 Annual Nameplate* Production Capacity Year End, 1976 (million kg) Plant 1 Total 570 280 80 70 70 70 260 210 50 250 180 70 220 110 70 40 200 180 20 180 110 70 170 90 80 21910019 BFG17034 k Table 4 (Continued) Company and Plant Location Union Carbide Corporation, Chemicals and Plastics Division South Charleston, West Virginia Texas City, Texas Certain-Teed Products Corporation Lake Charles, Louisiana The Goodyear Tire & Rubber Company, Chemical Division Plaquemine, Louisiana Niagara Falls, New York Robintech, Inc. Painesville, Ohio Georgia-Pacific Corporation Plaquemine, Louisiana Shintech, Inc. (joint venture of Robintech, Inc. and Shin-Etsu Chemical Industry Company, Ltd. of Toyko) Freeport, Texas Air Products and Chemicals, Division Calvert City, Kentucky Pensacola, Florida Inc., Plastics Occidental Petroleum Corporation, Hooker Chemical Corporation, subsidiary, RUCO, subsidiary Burlington, New Jersey Hicksville, New York The General Tire and Rubber Company Chemicals/Plastics Division Ashtabula, Ohio Point Pleasant, West Virginia Ethyl Corporation, Industrial Chemicals Division Baton Rouge, Louisiana 13 Annual "Nameplate3 Production Capacity Year End, 1976 (million kg) Plant | Total 160 ? 140 no 90 20 no 100 100 90 70 20 90 80 10 90 60 30 80 BFG17035 OZOOT6T2 Table 4 (Concluded) Company and Plant Location Rico Chemicals Corporation Guayanilla, Puerto Rico The Pantasote Company of New York, Inc. Eleanora Chemical Division Passaic, New Jersey Point Pleasant, West Virginia Great American Chemical Corporation Fitchburg, Massachusetts Atlantic Tubing & Rubber Company Cranston, Rhode Island Keysor-Century Corporation Saugus, California Total Annual Nameplate* Production Capacity Year End, 1976 (million kg) Plant I Total 70 60 30 30 30 20 20 3120 Actual operating capacities are usually somewhat lower. Published capaci ties are often larger because (1) the design presumes continuous produc tion of one type of resin whereas all producers make various types of resins in each plant, and (2) scheduled and unscheduled shutdowns are not taken into consideration in nameplate capacity figures. Source: SRI \ 14 BFGl'7036 H* CD K oO tv) In both of the ethylene-based processes, ethylene dichloride is first obtained and then is cracked to vinyl chloride and hydrogen chloride. In the oxychlorination process, ethylene dichloride is made by the reaction of air and hydrogen chloride with ethylene in a catalytic process. The catalyst is a mixture of copper chloride and other chlorides. In manufacture of vinyl chloride by direct chlorination of eth ylene, ethylene dichloride is first obtained by the catalytic vapor or liquid-phase reaction of ethylene and chlorine. Metallic chlorides, such as ferric, aluminum, copper, or antimony, are usually used as the catalyst. In the third process, which is still used by Monochem, Inc. at Geismar, Louisiana, vinyl chloride is produced by the reaction of acety lene with hydrogen chloride in the presence of mercuric chloride catalyst. Polyvinyl Chloride Resins Vinyl chloride, which is a gas at room temperature, is used in liquid form under pressure when it is polymerised to form PVC by one of the four basic processes: suspension polymerisation (accounting for the majority of total PVC produced); emulsion polymerisation; bulk polymerisa tion; or solution polymerization. In all processes, the polymerization is initiated by free radicals and proceeds at temperatures of 40-70sC with the evolution of heat. The term, polyvinyl chloride resins, includes vinyl chloride homopolymers with the repeating unit, -CH2CHCI-, and copolymers of vinyl chloride with varying amounts of another monomer (e.g., vinyl acetate, ethylene, propylene, vinylidene chloride, or acrylates). Suspension polymerisation is carried out in an aqueous system in which monomer droplets are maintained in suspension by means of a pro tective colloid in conjunction with brisk agitation. Generally, suspen sion polymerization is operated as a batch process employing glass-lined or stainless steel reactors. The reactor is first charged with deionized water, and then a protective colloid, a buffer, and an initiator are added. The vinyl chloride and, in the case of copolymer production, the second monomer are then intermittently introduced in controlled ratios. The mixture is brought to the polymerisation temperature (about 50*0, and after variable induction periods depending on the initiator used, the polymerization starts. The heat generated by polymerization is removed from the system to maintain the desired reaction temperature. The polymerization time can vary by as much as one-half (e.g., 8 vs. 16 hr) depending on the initiator used; in recent years, so-called co-initiation systems have reduced time in the reactor to about 6 hours. A dispersion of relatively large polymer particles in water is obtained by the suspension polymerization process. After unfeacted monomer is driven out of the slurry (and recovered), the slurry is cen trifuged, and the polymer is flash dried in an air stream at about 80*C. The dry polymer is screened and shipped, either in bulk or packed in multiwall paper bags. 16 BFG17038 Emulsion polymerisation is basically similar to the suspension process except that relatively large amounts of two emulsifying agents are used, one of which is soluble in the monomer, the other in water. This system very effectively prevents the coalescence of polymer particles, resulting in resins of a very small particle size. The drying methods (frequently by spray driers) are also designed to maintain a small parti cle size. Because complete removal of the emulsifiers is never achieved, resins made by this process are not used where high clarity is needed (such as in packaging films) or where low water absorption is required (such as in electric wire insulation). The initiator systems used in this process are different from those used in suspension polymerizationthey are typically redox-type, employing persulfates. In the bulk polymerization process, vinyl chloride is polymer ized without the addition oil other liquids. In this two-stage process, the initial liquid-phase reaction is followed by polymerization in an autoclave that is designed to agitate the then-dry, powdery mass effec tively until the conversion from monomer to polymer reaches a level of about 902. Heat exchange is provided by the distillation of monomer and its recondensation within the reactor and in external condensers. Bulk polymerized PVC resins resemble suspension resins in appearance and are characterized by high uniformity and purity of particles. In the solution rirstion process, the acnc-:.i-; ;.va Ziznz dissolved in an organic solvent (such as n-butane or cyclohexane) in an auto clave. After the addition of a peroxide initiator and heating of the stirred solution to about 40*C, polymerization begins, and the polymer precipitates as the reaction proceeds. Solution polymerization is used exclusively for the production of specialty copolymers of vinyl chloride with vinyl acetate. These copolymers are very pure and uniform, and their chief value lies in their unique solubility and film-forming characteristics. A significant trend in the polymerization processes for vinyl chloride has been toward larger reactors. Reactors typically have had a. capacity in the range of 7,570 to 28,388 liters (2,000 to 7,500 gallons), but reactors with capacities of 98,410 and even 132,475 liters (26,000 and 35,000 gallons) have been installed recently. (With a given amount of total plant capacity, larger reactors would probably reduce the total emission of vinyl chloride during the polymerization operation.) 219J.0024 Compounding of PVC Resins Polyvinyl chloride resins are compounded with'a number of auxil* iary materials before they are converted to end products. These materials include plasticizers, light stabilizers, heat stabilizers, pigments, and fillers. Compounding of PVC generally begins with premising followed by very intense mixing, because uniform distribution is mandatory for trouble* free processing and uniform product quality. Of the many types of PVC in use, most are relatively dry in the premix stage and have a free-flowing sandy consistency. To achieve intimate mixing, they are subjected to a hot mixing step at fusing temperature. 17 BFG17039 Conversion to End Products Compounded PVC resins are converted to end products by several processes. These include extrusion (about 53Z), calendering (about 18Z), dispersion (about 13Z), injection molding (about 6Z), compression molding (about 4Z), coating and adhesives (about 4Z), and blow molding (about 2Z). Figure 3 shows the production and use of vinyl chloride. Emissions and Their Sources The areas of potential for human exposure to emissions of vinyl chlo ride may be ranked as follows: When vinyl chloride is polymerized to form PVC--the major emission source and the process in which the highest occu pational exposures have been recorded. Production of vinyl chloride itself--the three current man ufacturing processes for this are not ordinarily serious emission sources of the monomer. Fabrication of PVC products--a possibility for emissions and exposures, though not a major one, arising when unre acted, entrapped monomer is released during the fabrica tion process. The general environment and miscellaneous sources--includ ing irhslatic" - contaminated air in the neighVor^rod of a plant; ingestion of food or water contaminated wich vi nyl chloride that has migrated from pipe, containers, or wrapping; or, until 1974, inhalation resulting from use of aerosol containers containing the gas as a propellant. Polymerization of Vinyl Chloride to PVC As indicated above, it is the polymerization process that is the largest emission source. The Environmental Protection Agency (EPA) has estimated that 83Z of U.S. emissions emanate from PVC production facilities.3 Most occupational exposures occur in the area of the polymeriza tion reactors. They have been especially high during the hand cleaning of reactors to remove accumulations of PVC scale on the reactor walls. This hand-cleaning procedure was common until the mid-1960s, when cases of acroosteolysis led to the development of high-pressure spray washers; it continued in some plants until the implementation of the OSHA Temporary Standard in early 1974, often without provision of protective equipment. The task was usually assigned to the newest employees, so that nearly all workers employed in polymerization plants before 1960 were given this 18 BFG17040 21910025 19 BFG17041 N K Cfi K O O a FIGURE 3 PRODUCTION AND USE OF V IN Y L CHLORIDE experience. This task is still required intermittently, because of lack of complete removal of scale by the washers, but it is currently performed only by workers in impervious isolation garments, with adequate respira tory protective equipment. Exposures during the hand-cleaning operation, which requires climbing through a manhole into the reactor vessel, were commonly several thousand parts per million. In addition, it has been estimated that gen eral exposure levels in the PVC plants during the 1940s and 1950s were "...frequently over 1000 ppm and commonly in the 100 ppm range.... Current exposures are dramatically less than those past exposures as a result of nearly universal industry compliance with the requirements of the OSHA Standard. Daily time-weighted-average occupational exposures have been reduced to levels near to or below 1 ppm for most workers, al though such exposures to 10 ppm are not uncommon.5 The greatest exposures continue to be experienced by the reactor operators, operator's helpers, workers who transfer the incoming vinyl chloride monomer to storage vessels, maintenance personnel, and workers in the compounding steps. The sources of vinyl chloride emissions at a typical PVC plant and their relative contributions to the total uncontrolled emissions are shown in the following tabulation:^ Source Fugitive emission sources(leakage, loss during sampling, vaporisation Ti'.'u: wastewater, and the like) Sources following the stripper(blind tank, dryers, bulk storage, and the like) Monomer recovery system Stripper Relief valve discharge Reactor opening Percent of Total 392 322 132 82 52 32 1002 21910027 Production of Vinyl Chloride Monomer The three production processes for the commercial manufacture of vinyl chloride are not ordinarily serious emission sources of Che mono mer. The EPA estimates that 112 of all emissions can be attributed to these plants.3 20 BFG17042 Occupational exposures generally occur after production, as the finished monomer is piped to storage or transportation, or during maintenance. Data reported to OSHA on exposures before the emergency temporary standard was imposed indicated peak exposures over 200 ppm for laboratory technicians, oyer 150 ppm for loading operations, and near 50 ppm for quality control specialists.4 The following tabulation shows some levels found in a recent survey, conducted for N10SH, of three vinyl chloride plants in which it will be noted that time-weighted-average ex posures range from 0.07 ppm to 26.46 ppm:6 Job Category VCM Breathing Zone Concentration Ranges (ppm) Single Measurement Time-Weighted Average Loader Plant operator Lab technician Chromatographer Shift supervisor Pipefitter Instrument man 0.06-84.77 0.01-18.2 0.03- 4.36 0.02- 1.01 0.03- 0.55 0.01- 0.41 0.02- 0.25 0.30-26.46 0.07-11.03 0.07- 0.40 0.06- 0.28 0.09- 0.11 0.17- 0.30 0.17 The sources of vinyl chloride emissions from a typical viuvl chloride monomer plant and their relative contributions to the total uncontrolled emissions are shown below:3 Source Percent of Total Vinyl chloride formation and purification 54Z Fugitive emission sources 271 Ethylene dichloride purification m Oxychlorination reactor 81 100Z 21910028 Fabrication of PVC Products The fabrication of final products from intermediate PVC stock has not been considered a serious source of either emissions or exposures. (Neither EPA nor OSHA has included fabrication plants in its regulations.) In large part, this has been due to uncertainty as to the extent and na\ ture of exposures during fabrication processes and emissions from them. Both agencies are currently attempting to define the contribution of 21 BFG17043 fabricating plants to the occupational and environmental exposure burdens. That there may be a potential problem is evidenced by two cases of angio sarcoma known in workers who had occupational exposure only in fabrication.7 The most severe exposures and emissions would be expected at those faorications plants where unblended PVC resin is received and then carried through to fabrication of the final product. The personnel most likely to be exposed are those working in the blending and compounding processes, where the PVC resin is heated and mixed with additives. These processes present an ideal opportunity for the release of any unreacted vinyl chloride monomer that may be present in the PVC. Employees working in storage areas may also be exposed to vinyl chloride released from poorly stripped resin. The NIOSH survey mentioned above& also covered fabrication plants. About four-fifths of the samples from time-weighted-average exposures were below 0.01 ppm, which was the lower detectable limit of the sampling and analytical method used. However, there were substantial ihterplant, as well as intraplant, differences, with exposures in similar job categories ranging from less than 0.01 to 2.44 ppm. The time-weighted-average con centrations of vinyl chloride for various job categories at the seven fabrication plants in the survey are shorn in the following tabulation: Average Concentration Job Classification______ (ppm) Calender personnel Pelletizer personnel Compounding personnel Laboratory personnel Molding personnel Plastisol dipping personnel Extrusion personnel Maintenance personnel Miscellaneous personnel 0.85 0.55 0.16 0.C3 0.02 0.01 0.01 0.01 0.01 Since vinyl chloride emissions from fabricating plants result from residual monomer in the raw material coming from PVC. plants, they will be minimized indirectly as vinyl chloride is controlled more closely at the PVC facilities. N General Environment and Miscellaneous Sources Current exposure pathways of vinyl chloride to the general pub lic are through inhalation of contaminated air in the neighborhood of a plant or through ingestion of contaminated food or water. Also, there are some miscellaneous minor exposures that may arise in the occupational or general environment; they include the disposal of partially polymerized 22 BFG17044 r waste sludge and occupational exposures during the use of vinyl chloride to produce methyl chloroform or the production of vinyl chloride as a by product . Gaseous vinyl chloride emitted into the air at vinyl chloride and PVC plants is estimated to account for 96Z of all atmospheric emissions of the monomer.3 It is distributed into the atmosphere surrounding the emission source in patterns and amounts that depend on the process in volved, the amount of vinyl chloride produced, the nature of the plant area from which it is released, topography, and meteorological conditions. Preliminary monitoring results in 1974 at seven industrial com plexes involving ten PVC resin and two vinyl chloride plants indicated that the levels of vinyl chloride in the ambient air near the plants fluc tuated sharply. This was apparently due to the periodic opening of reac tor kettles in the PVC plants, accidental plant discharges, variations in the production process, and meteorological conditions. While almost all of the samples collected contained detectable levels of vinyl chloride, more than 90Z of the instantaneous observations and 97Z of the 24-hour samples show amounts less than 1 ppm. Although a level of 33 ppm was found in one sample at one PVC plant, repeated sampling indicated that this level was unusually high and that the average at this site was less than 1 ppm.8 A.though meet samples were obtained within one-half mile the plant, in one case a level of 3.4 ppm was recorded at a distance of three miles from the plant. However, the average of several readings at this site was approximately 0.5 ppm. The EPA has estimated average exposures to the 4.6 million people who live within 5 miles of vinyl chloride plants at 0.017 ppm.9 Vinyl chloride levels in the air in the general community are usually below detectable levels, and the EPA has estimated general average population exposure at 0.5 ppb. Inhalation of vinyl chloride, based on the assumption of 20 m3 of air inhaled per day containing 0.5 ppb vinyl chloride, is 0.03 mg/day.8 In a 1973 EPA study of combustion products from the incineration of plastics, vinyl chloride was identified in the flue gas from incinera tors. 10 The quantity of vinyl chloride from a representative PVC homo polymer varied as a function of temperature, as shown in the tabulation below: Combustion Product--Vinyl Chloride (in mg/g of sample polymer) 25-280C 280-350*C 350-430*0 430-510*0 510-580C 0.04 0.25 0.17 0.02 -- 21910030 23 BFG17045 The, quantity of vinyl chloride also varied with the form of fabricated plastic article but was primarily dependent on entrapped monomer concen tration and temperature. Measurements of the concentration of vinyl chlo ride in the ambient air in the vicinity of municipal incinerators have not been made. Exposures through consumer products, such as cosmetics, and through foods and beverages are dependent on the migration rates of vinyl chloride from PVC containers and products. However, very few data exist to show such migration. It is believed that the extent of migration de pends upon the residual monomer in the PVC containers, the length of time of storage, and the industrial processes used. The total oral daily human intake of vinyl chloride for Europeans has been estimated at less than 100 ^g,H and, according to the World Health Organization, intake of vi nyl chloride from food may be on the order of 1 pg per person per day.12 The preliminary report of the range of vinyl chloride concentrations in some consumer products reported by the U.S. Food and Drug Administration is shown in Table 5.13 These data are not adequate to determine a dietary exposure to vinyl chloride. In an EPA survey of 80 public water supplies in 1974, small quantities (between 0.27 and 5.6 ppb) of vinyl chloride were found in three of four samples from the municipal water supplies of Miami and Phil adelphia.^ xhe sources of the substance have not been identified. EPA and FDA are undertaking test programs to determine the mi gration of vinyl chloride from PVC water pipe. The results so far show that migration of residual vinyl chloride does occur and that the extent of the migration depends on the residual level in the PVC. Waste effluents from vinyl chloride and PVC plants were moni tored for vinyl chloride. Levels were found to vary considerably depend ing upon the in-plant handling of wastes and treatment of wastewater. The highest level of vinyl chloride found in wastewater leaving the plant site was 20 ppm. More typically, levels of 2 to 3 ppm were found. The levels of vinyl chloride entrapped in sludge and other solid wastes from the reactor kettles ranged from 100 ppm to, in one case, 3000 ppm.6 With regard to other miscellaneous sources of vinyl chloride emissions--sources that either use vinyl chloride for production of methyl chloroform or that produce vinyl chloride as a by-product--preliminary reports indicate that there are eight such plants in the United States and that they account for approximately 3Z of the total estimated 1974 emissions from all sources.13 The EPA has not proposed vinyl chloride emission standards for these plants. Dispersion and Degradation of Vinyl Chloride In the paragraphs that follow, the ultimate dispersion and degrada tion of vinyl chloride in the atmosphere, water, and soil is discussed briefly. 24 BVGn46 21910031 Table 5 RANGE OF VINYL CHLORIDE CONCENTRATIONS IN SOME CATEGORIES OF CONSUMER PRODUCTS Product_______________________ Range*__________ Senaitivity Cosmetics** N.D.C to 4 ppm 0.1 ppm Mouthwashes^ N.D. to 7 ppm 0.05 ppm Biologic products Vinegar N.D. 0.02 to 0.4 ppm N.D. to 8.4 ppm Unknown Oil 6.5 to 10 ppm Unknown Meat products N.D. to 0.4 ppm Unknown Water pipe (residue) 1 to 100 ppm 0.05 ppm : PVC films 1 ppm ro 4 ppm Unknown Sheeting 1 ppm Cap liners (food and beverage jars) N.D. Unknown -- preliminary data--not verified by Food and Drug Administration. bTime in bottle--3 to 48 months. cNot detectable. dAll samples purchased before November 1974. Source: Chapter reference 13 21910032 Atmosphere Vinyl chloride boils at -13.9*C and thus is a gas at normal at mospheric pressure. It is slightly more than twice as dense as air* Results on the atmospheric reactions and rates of disappearance of vinyl chloride in the ambient atmosphere are inconclusive. The peak absorption of the substance in the ultraviolet region is far below the solar cutoff (approximately 290 nm), so that vinyl chloride would not undergo reaction in sunlight in the absence of other reactive chemical species. 25 BFG17047 Laboratory photochemical chamber experiments have shovn differ ent photodegradation rates of vinyl chloride in the presence of high con centrations of different reactants (including NO2, 03, and NO) that are commonly found in ambient air. The half-life of vinyl chloride was re ported to be 3 to 6 hours, and the reaction products identified included carbon monoxide, formaldehyde, formic acid, formyl chloride, and hydrogen chloride.13 Two chemical reaction mechanisms that appear to be potentially important for removal of vinyl chloride in ambient air have been identi fied. They are: Reaction with HO* radical, which is most often present at 4 parts per trillion (10~14 molar) concentrations, and Reaction with ozone (O3) usually found in the range of 10-100 parts per hundred million (4 - 40 x 10"9 molar).17 The concentration of vinyl chloride in the immediate vicinity of emission sources may be sufficiently high to deplete the photochemical oxidants, and under these conditions the substance can be considered a stable pollutant. Under strong nocturnal inversions during the fall and winter, buildup of vinyl chloride from emission sources may thus be of particular concern. The half-life of vinyl chloride in more "typical" am bient conditions has not been measured but is estimated at about 20 hours. * Water and Soil The solubility of vinyl chloride in water is 1.1 g/liter. The quantity (up to that limit) that dissolves in water will depend upon the partial pressure, or concentration, of the gas above the solution. If the partial pressure of the vinyl chloride gas above the water is reduced-- for instance, if a stream runs from an area with high airborne concentra tions of vinyl chloride to a less contaminated area--vinyl chloride will escape into the air. The rate of bulk exchange of gaseous vinyl chloride between atmosphere and water is about twice that of oxygen, and thus the escape will be rapid.! Preliminary results of EPA investigations support the suggestion that vinyl chloride will escape rather quickly from agitated or aerated water at room temperature. Half-lives ranging from about 5 minutes to about 5 hours were observed. There was no significant difference in the rate of vinyl chloride losses from distilled water, river water, or vinyl chloride plant effluents stirred at similar rates.19 In addition to the bulk exchange of gaseous vinyl chloride be tween air and water, the chemical reactions of vinyl chloride in water have been considered. These can include reactions with water impurities or the processes of hydrolysis, oxidation, or photolysis and might act to increase or decrease the residence time (and environmental availability) 26 BFG17048 21910033 of vinyl chloride in water. Certain metal ions do have the ability to combine with vinyl chloride; for example, soluble silver and copper salts increase the solubility of vinyl chloride in water by forming complexes. Under environmental conditions, however, few of the complexation reactions are expected to be important. The estimated half-lives for hydrolysis and oxidation of vinyl chloride in water are relatively long (see Table 6), and photolysis is considered an unimportant mechanism for loss of vi nyl chloride in water. Vinyl chloride may persist long enough to accumulate biologi cally via direct absorption or via the food chain. This might result from the slow, continuous release of vinyl chloride from sediments and sludges, combined with either a continuous input of vinyl chloride into water or poor, erratic mixing in lakes or ponds. However, data are not yet avail able to indicate the extent (if any) of inorganic particulates, and sorption to bacteria, algae, or fungi has not been detected. Bacterial degradation of vinyl chloride was found to be negligible, and vinyl chloride did not affect bacterial growth under test conditions in aqueous systems.18 Microbiological degradation of vinyl chloride in soil may be of significance in depletion of vinyl chloride over long time periods. However, information regarding such biodegradation is not available. From the above, it can hi* ?'-*> '.re nost inportr'"* mecha nism tor removal of vinyl free water is volatilization and that other mechanisms are of limited potential importance. It can also be seen that vinyl chloride will have a limited potential for general envi ronmental effects as a water pollutant, principally because it is removed so rapidly and dispersed into the air. This suggests that inhalation of vinyl chloride in air is likely to be the most important exposure pathway for the general public, as it is for those persons who are occupationally exposed. Source/Exposure Model Figure 4 presents a conceptual model based on the foregoing estimates for the flow of vinyl chloride from emission through the environment to man. The model is qualitative, with exposures based on empirical and estimated data. Table 7 shows the relative importance of vinyl chloride exposure for people in different environments. In Figure 4 and Table 7, the need for control of airborne emissions to limit exposures of humans is indicated, even for the general public (i.e., those persons not occupationally exposed). 21910034 27 BFG17049 ESTIMATED ENVIRONMENTAL PERSISTENCE OF VINYL CHLORIDE 4ue0410C41>O*) ON CM Ncs mCM CM o0s) 4p0p44>4 44 00 wtoo Cw00O1) . o x0 U > 44 GO o4 S K co X o n tn o o6O 44cto44 OptQoS) um 'xwo' r*1o*> a X pIi o + X 1^o4 CM oX 1 poH a oX O1N opH K CM a m o o4uCctcoo4O H0t0u1o)) o 6 0) u O1On pH oH *4 ON o o CpoMH 4to4 404) OS p4 Hoc 44 Uto OVS tHo CO v o u >os tHo 00 >% *owo >N 4ptcoo44 o K XXO fcoH 4to4 u Xp4 o co 4pJ4 to 73 oXp4 Ct0oO) flu U 44toJ X u V 4toJ X u X4toJ u p4 < u <H CO OC p4 4to4 4w4 c ooco V u 4cto4 uto 04*) w tto0h 28 2191003 BfGV705 in z' ! ft P> CJD V-: O o29 O) BFG17051 <5) C tm r il Public P to p lt 3 H llt trow F U n ti e I i II r Ir si t M s & t oo <8e ~ ?vt ____________________ W orker* (Tim e-W eighted-Average E s p o s ufrfti)l r i c i t o n VCM ~ S o u rn - o t KxfHsnri> oi. *--e*i* &iar*rivg* e -- 8o use aa. *n* . c* qe wc --o ---- --vc euv ucc wi> b E b q k * TC>l & ---- g e *. --e ye <> *5 c0 <*V 30 BFG17052 *0 H* C h* oO CO si Chapter III NONCARCINOGENIC EFFECTS OF VINYL CHLORIDE Animals, Microorganisms, and Plants In addition to tumorigenesis, other biological effects of vinyl chlo ride have been observed in several different animal species, microorgan isms, and plants. Effects of vinyl chloride and polyvinyl chloride (PVC) and the byproducts of their production have been studied to determine toxicity, mutagenicity, metabolism, and teratogenicity. Animals Animals exposed by inhalation to anesthetic doses of vinyl chlo ride have exhibited tracheal irritation, cardiac irregularities, pulmonary edema, and hyperemia of liver and kidneys.1 Animals acutely and chroni cally exposed to vinyl chloride by inhalation have been found to have in creased liver weight, interstitial hepatitis, central lobular degeneration of the liver, fibrosis and necrosis of the liver, degeneration of bone, of connective tissue, and of nerves, and chronic interstitial nephritis.23 These effects of exposure are seen predominantly in male animals. Systemic aberrations, which may be precursors to angiosarcuma, are observed in the vasculature of essentially every tissue and organ in the body.^ Chronic effects include increased blood epinephrine, fibrosclerosis of the vessels, and hypertension.5 These systemic vascular effects are very similar to the vascular effects seen in humans. The systemic vascular effects appear in correlate with the systemic distri bution of angiosarcoma in both animals and man. It is not known whether vinyl chloride or some metabolite may be responsible for the observed vascular effects in animals and man, although a metabolite(s) of vinyl chloride is suspected to be involved in carcinogenesis. A wide range of agents increase the toxicity of vinyl chloride. Pretreatment with phenobarbital, ethanol, polychlorinated biphenyls, or certain pesticides (i.e., hexachlorobenzene) increases liver injury in animals subsequently exposed to vinyl chloride.! Mutagenesis Vinyl chloride may be mutagenic,6,7,8 but the issue has not been resolved. Using bacterial mutagenicity tests, some investiga tors have observed equivocal results from tests with and without liver 31 BFG17053 8E00T6TZ microsomal preparations. Such results do not resolve the question of possible metabolic activation by bacterial enzymes. Following metabolic activation, vinyl chloride is mutagenic. The metabolites involved may be chloroethylene oxide, chloracetaldehyde, or chloroethanol.7,9,10,11 The metabolites may act as alkylating agents similar to bis-chloromethylether, a strong mutagen as well as a carcinogen. Chloroethylene oxide may be produced from vinyl chloride by the mixed function oxidase system (MFOS). Chloroethanol and chloracetaldehyde may be produced from vinyl chloride via chloroethylene oxide or independently by an alcohol dehydrogenase pathway. In rats, the latter pathway appears to be operative at concentrations below 50 ppm. The MFOS is apparently not a major pathway for vinyl chloride metabolism until inhalation expo sures approach 200 ppm. Teratogenesis To date, little experimentation has been performed to investigate the deleterious effects of vinyl chloride on embryonal and fetal development, and there is no unequivocal evidence for or against teratogenic action. Fetal effects were studied in three animal species by maternal inhalation at several concentrations.12 To assess the pos sibility that ethanol might alter the metabolism and thereby enhance the toxic or teratogenic potential of vinyl chloride, some animals were simultaneously exposed to 157. ethanol in drinking water. Both maternal and embryonal toxic effects were induced. Also, though gross structural malformations were not observed, minor skeletal abnormalities occurred in excess among mice exposed to 50 ppm with ethanol and to 500 ppm with a-d without ethanol, and among 'ats exposed to 2500 ppm with ethrncl. Microorganisms and Plants No adverse effect has been demonstrated on plant growth when PVC piping has been used for irrigation. However, numbers of soil bac teria are reduced and nitrifying bacteria are increased.13 Studies have shown that vinyl chloride causes injury to plants in a manner similar to ethylene.1^>1^ Byproducts from vinyl chloride production dumped into the ocean affect the early development of marine life.16,17 Vinyl chlo ride byproducts accumulate in marine animals,18 as do other chlorinated compounds such as DDT and polychlorinated biphenyls. Furthermore, vinyl chloride byproducts have been shown to increase bacteria cell membrane fragility, which has been postulated as a mechanism of disease in higher animals, including man.19 32 BFG17054 21910039 Toxicity to Humans It has long been recognized that vinyl chloride gas is capable of producing acute toxic effects in humans. However, a full understanding of the nature and extent of its chronic toxicity has been years in un folding and has come almost exclusively from observations among occupa tionally exposed individuals. Major nonmalignant effects clearly associated with occupational ex posure to the gas include: acute intoxication; disturbances of liver function; acroosteolysis, often with Raynaud's phenomenon, and sclero derma; and alterations in pulmonary function, with or without abnormal chest x-ray findings. Other effects, such as alterations in the cellular elements of the blood have been reported among vinyl chloride workers by some authors, but confirmation by other authors has not been uniform. Finally, there is some evidence that workers exposed to vinyl chlo ride may exhibit an increased frequency of chromosomal aberrations; that wives of vinyl chloride workers may experience an excess fetal death rate; and that mothers living in communities near PVC-production facilities may be at an increased risk of giving birth to children with birth defects. It must be emphasized that, at the time of this writing, a causal rela tionship between vinyl chloride exposure and these latter phenomena--chro mosomal aberrations, excess fetal death rate, and birth defects--has by no means been established. Acute Intoxication Vinyl chloride gas is an anesthetic which is slightly irritat ing to the moist membranes of the eyes and respiratory tract. Its not unpleasant odor can be detected by some at concentrations as low as 300 ppm, but others cannot detect its odor until the gas reaches much higher concentrations. It has been reported that workers exposed to vinyl chlo ride gas can detect its presence at concentrations below the odor threshold because it produces a sensation of tingling and heat over the skin of the lower extremities. As the concentration of gas increases, those exposed may become mildly euphoric and, at still higher levels, a typical syndrome of ine briation may appear.^ When anesthetic concentrations of the gas are reached, about 7Z, narcosis develops rapidly and may terminate in death due to respiratory failure. The use of vinyl chloride as a surgical anes thetic was considered in the 1930s, but apparently it was never used for this purpose in humans. The ability of the gas to produce cardiac ar rhythmias was later recognized, at which time it was recommended that it not be considered for use as a surgical anesthetic in man.50 Two accidental fatal poisonings attributed to occupational ex posure to vinyl chloride gas were reported in 1950.22 Both fatalities occurred in PVC polymerization workers, one who was overcome by the gas while cleaning out a reaction vessel, and the other while inspecting a BfGVl055 21910040 tank containing effluent from the polymerization process. Both victims were discovered within a few minutes after having been in contact with fellow workers, suggesting that they had encountered very high concen trations of vinyl chloride gas and collapsed immediately. The autopsy findings in both cases were similar but nonspecific, consisting primar ily of congestion of internal organs and failure of the blood to clot. In 1963, six human volunteers were exposed to concentrations of vinyl chloride gas up to 20,000 ppm.23 Exposure periods were limited to five-minute periods, twice daily, separated by a six-hour interval and continued for three successive days. At concentrations about 8,000 ppm, acute toxic effects including dizziness, nausea, headache, and di minution of vision were observed. Disturbances in Liver Function Workers chronically exposed to vinyl chloride gas may exhibit disturbances in liver function as well as alterations of liver structure. Functional disturbances are nonspecific in nature and often fail to reflect the true extent of structural damage.40,42 Several investiga tors, 30,31 have suggested that this may be explained by the observation that the principal anatomic lesion of vinyl-chloride-induced liver dis ease is fibrosis, with relative sparing of the functional cells of the liver, the hepatocytes. One investigation31 for example, after examin ing the microscopic structure of liver tissue from patients with vinylchloride-related liver disease, with and without angiosarcoma, reported the presence of a "peculiar" hepatic fibrosis but noted that the hepato cytes were not severely injured. Notwithstanding this phenomenon of hepatocyte sparing, it is apparent that ultimately these functional cells become involve'' Ir. the disease process t-,, extent that can be detected by conventional tests of liver function such as dye excretion studies (bromsulphalein and indocyanine green) and plasma enzyme activities (serum glutamic oxaloacetic transaminase [SGOT], serum glutamic pyruvic transam inase [SGPT], alkaline phosphatase).20,25,29,30,32,33,40,41,42 Creech and his colleagues29,41,43 have emphasized the impor tance of persistent biochemical abnormalities in the assessment of vinylchloride-mduced liver damage. They conducted a program of medical ex aminations including a battery of liver function screening tests on 1,183 PVC plant employees, 309 of whom worked directly in PVC production areas. On the initial examination, 26Z of the entire group of 1,18.3 study par ticipants had one or more abnormal liver function test result. The per centage of production area employees with abnormal liver function teat results did not differ from the overall group experience in this initial screening program. However, on repeat examination of employees who had one or more abnormal liver function test results on the initial screening, persistent abnormalities were almost three times more frequent among PVC production area workers than among those in areas not directly related to PVC production (11Z vs. 4.5Z). 34 ^G\1056 21910041 r 'i Vinyl-chloride-related alterations of liver structure have been demonstrated by hepatic arteriography ,44 46 radioisotopic scintiscan tech niques,^ 46 peritoneoscopy,45 and by direct examination of biopsy and autopsy specimens.30,31,41,47 Although each of these procedures can pro vide useful information on the nature and extent of liver involvement, at the time of this writing none is considered, of itself, to be specifically diagnostic (pathognomonic) of vinyl chloride injury. Clinical manifestations of portal hypertension, such as hemor rhage from esophageal varices may accompany vinyl-chloride-induced liver injury as may pronounced spenomegaly. Acroosteolysis In the early 1960s, a symptom complex consisting of a Raynaud1s- like phenomenon involving the hands, scleroderma-like changes in the skin of the hands and forearms, and osteolytic and sclerotic lesions of the bones of the extremities and sacroiliac joints were described by a number of authors in this country and elsewhere.24,25,26 This symptom complex was called occupational acroosteolysis and appeared to be confined to workers engaged in cleaning PVC polymerization reactor vessels. The pe riod from the beginning of exposure to the first symptoms was found to be as short as one month or as long as three years.27 A year or two after ' tho;. affected had been Temoved from exposure, most oi abnormalitiet disappeared, and the bones showed signs o healing. The authors of one study*" believe the cause of occupational acroosteolysis to be a combination of three factors: chemical insult, physical insult, and, due to the relatively low incidence of the disease among those exposed, personal idiosyncrasy. In a personal communication, one of the coauthors of the study. Dr. John L. Creech, expressed his be lief that occupational acroosteolysis was not caused by vinyl chloride gas itself, but rather by vinyl acetate, which is formed as a condensa tion product. in the reaction vessel when vinyl chloride polymer is heated. The relationship, if any, between occupational acroosteolysis and vinyl-chloride-induced liver disease is unclear. Changes in the Lung Both radiographic and functional changes of the lung have been reported in vinyl-chloride-exposed workers. m One group of investigators^ obtained spirometry and maximum expiratory flow volume curves in 348 workers in a vinyl chloride polymer ization plant. Their major finding was decrease in air flow in over 50Z of the workers examined. This abnormality correlated with age and dura tion of exposure. A relationship with smoking was noted only in younger workers with exposure of less than ten years. Among workers aged 40 and 35 BFG17057 21910042 over, and among workers with exposure of more than 20 years, the preva lence of this impairment was similar in smokers and nonsmokers. The au thors suggested this to be evidence that occupational, or other factors aside from smoking, were operative. Another team of scientists^ conducted a survey of vinyl chlo ride polymerization workers which included chest roentgenograms, a com plete smoking history, a chronic bronchitis questionnaire, and pulmonary function studies. They noted a definite increase in roentgenographic changes associated with length of exposure to vinyl chloride. These changes were primarily comprised of small linear reticular and rounded opacities. The prevalence of positive smoking history was found to be higher in workers with abnormal chest roentgenograms. No statistically significant difference was found between chronic bronchitis as diagnosed by questionnaire and abnormal chest roentgenograms. Pulmonary function studies showed obstructive changes in almost half of the workers examined. No correlation between chest roentgenographic changes and pulmonary func tion abnormalities could be established. The abnormalities observed prompted the authors to suggest that a similar mechanism may be active in the pulmonary tissue of vinyl-chloride-exposed workers as is recognized at other sites. Hematologic Changes Hematologic changes among vinyl chloride workers have been re ported by several authors. The most striking changes have been those re ported by investigators from the Federal Republic of Germany (FRG).32,33,48 One group32 found that 812 of 70 patients examined exhibited slight to severe thrombocytopenia, independent of the presence of splenic enlarge ment ,nd accompanied by normal bone marrow morphology. They hypothesized thac these findings were the result of tnrombocyte destruction not only in the spleen, but at other sites as well. Another group of investigators, reporting from the U.S.A., noted the FRG reports of thrombocytopenia but found only one such case in their series of 354 vinyl chloride workers.35 Other hematologic changes in vinyl chloride workers have also been reported, including anemia,20,35 leukopenia,^32>35 and reticulocytosis.32,48 for the most part, however, these findings have represented only infrequent, minimal deviations from normal values. Chromosomal Aberrations. Excess Fetal Death Rate. and Birth Defects Chromosomal aberrations,^ increased fetal death rate,^ and birth defects36 have all been reported as possible effects of occupational or community exposure to.vinyl chloride. In one study,^9 chromosome analyses were conducted on seven men occupationally exposed to vinyl chloride and on three control subjects, all of whom worked in the same plant. The seven exposed subjects had 36 BFGn058 21910043 worked with vinyl chloride for 7-29 years. Periodic clinical examinations had showed no evidence of acroosteolysis or liver dysfunction. Chromo somal analyses of cells from the exposed and control groups revealed 9.52Z and 1.94Z aberrations, respectively. This difference was found by the authors to be significant (<0.001). Stimulated by reports^'3 that vinyl chloride is mutagenic in microbial test systems, a team of investigators examined the pregnancy outcome among wives of workers exposed to vinyl chloride.28 These investi gators compared fetal death rates prior to and subsequent to the husband's exposure to vinyl chloride. They found that prior to the husband's expo sure, fetal death rates (6.1Z) were similar to a control group (6.9Z) not exposed to vinyl chloride, but subsequent to exposure, fetal death rates were significantly increased (15.8Z) when compared both with the control group and with pre-exposure rates. The authors postulated several mechanism by which fetal loss might be related to vinyl chloride exposure. They considered fetal tox icity or germ-cell mutagenesis in the mother through indirect vinyl chlo ride exposure from the father unlikely because the high volatility of vi nyl chloride would preclude its being inadvertently transported from the workplace to the home via clothing, etc. They considered the leading possibility to be germ-cell damage in the father as a direct consequence of vinyl chloride exposure in the workplace. Several technical weaknesses heavily becloud the'validity of the results reported in this study. No interviews were conducted with work er's wives; data on total number of conceptions and pregnancy outcome were ascertained by interviews with male employees. Moreover, according to the authors "no data were obtained concerning maternal age, except indirectly through paternal age." Lastly, although as correctly pointed out by the authors, fetal loss is known to increase with increasing pa ternal age, in this study the results were directly the opposite. The fetal death rate was higher among wives of husbands less than 30 years of age than among wives of older .workers (20Z vs 13Z). In a later communi-___ cation,39 the authors suggested that if vinyl chloride exposure were truly associated with the observed excess in fetal mortality, the greater effect in younger workers could, in theory, reflect the placement of younger workers in less desirable work exposure situations for seniority reasons. Nonetheless, the implications raised by this report must be considered highly speculative until additional supporting evidence can be developed. A studyof residents living in communities adjacent to vinyl chloride facilities revealed an excess number of congenital malformations when compared to vital statistics data from both the state and the balance of the counties in which the communities were located. This excess in cluded defects of the central nervous system, genital organs, and upper alimentary tract. A significant excess of club foot was also observed. The authors could not attribute the noted excess to race, maternal age, or regional differences in reporting of birtn defects. 37 BFG17059 Z1910044 This study has many important limitations. Ho information on ambient air levels of vinyl chloride was presented, nor was consideration given to other factors that are known to contribute to the incidence of congenital malformations, such as infectious agents, other industrial exposures, background radiation, or genetic factors. A subsequent study by the U.S. Public Health Service, Center for Disease Control's hospital-based birth defects monitoring program^ confirmed a moderate increase in central nervous system congenital mal formations in one of the communities included in the above investigation. None of the interviewed parents of affected infants had ever worked at either of the two vinyl chloride plants located in the community, nor did they live within two miles of either plant. The investigators concluded that, in their study, they could find no association between vinyl chlo ride exposure and congenital malformations. i 38 BFG17060 21910045 Chapter IV CARCINOGENICITY OF VINYL CHLORIDE Animal Studies There exists adequate experimental evidence to confirm that vinyl cnlorioe is carcinogenic in mice and rats when administered by inhalation. A dose-response relationship has been indicated in mice receiving doses of 50 to 10,000 ppm of vinyl chloride. The tumors observed in mice are predominantly liver angiosarcomas, mammary adenocarcinomas, and lung adenocarcinomas. Other types of tumors have also oeen observed. In rats, the tumors observed are predominantly liver angiosarcomas, Zymbal gland tumors, nephroblastomas, lung adenocarcinomas, and osteo chondromas. At the lowest level of exposure, 50 ppm, a single nephroolastoma and a single liver angiosarcoma were observed in rats. The fre quency of these and the other tumors increased with increasing levels of exposure. There is also evidence that vinyl chloride is carcinogenic in rats by both transplacental and oral routes of administration. Finally, preliminary insults indicate ihe carcinogenicity of vinyl chloride m hamsters following lunalational administration. Liver angio sarcomas as well as skin epitheliomas, lymphomas, and melanomas have been observed in experiments still in progress. Mice In mice receiving doses of 50 to 10,000 ppm of vinyl chloride the tumors observed were primarily lung angiosarcomas, mammary aoenocarcinomas, and lung adenocarcinomas (Table 8).l . _ _ in a suDsequent report on the progress of the same experiment,^ additional tumors were observed including subcutaneous angiomas, skin squamous carcinomas and acanthomas, renal angiosarcomas, hepatic angio mas, liver fibroangiomas, one heart fibroangioma, and an ossifying inter scapular angioma (Table 9). In a related inhalation study, a total of 200 mice of both sexes (CD1 bwiss Cnarles River) were exposed to either 0, 50, 200, or 2,500 ppm of vinyl chloride vapor for seven hours per day, five days per week for nine months. Preliminary data were published following eight months of exposure. At this time, when tissues from only a few animals had been 39 BFG17061 21910046 ( INCIDENCES OF TUMORS IN MICE EXPOSED TO VINYL CHLORIDE FOR 30 WEEKS AND DYING WITHIN 34 WEEKS uoocVe u>X o J o em 4>> ec eo > *o4 * so s 4> c 4u) 14*>4 C4** U 44J) Cl JtCo u uco 4U) M9O 40 <v. BFG17062 21910047 INCIDENCES OF TUMORS IN MICE EXPOSED TO VINYL CHLORIDE FpR 37 WEEKS AND SURVIVING UP TO 41 WEEKS twouu3o 41 BFG17063 21910048 examined, a dose-response relationship was observed in a number of mortal ities with neoplasms. The tumors observed at all dose levels included lung adenomas, liver angiosarcomas, and mammary gland adenosquamous car cinomas. The number of each of these types of tumors increased with dose. At the time of publication, no tumors of any type had been observed grossly in any of the untreated control mice.^ Rats An inhalation study was performed in rats in which a group of 26 males (Wistar) was exposed to an atmospheric concentration of 30,000 ppm of vinyl chloride for four hours per day, five days per week, for 12 months. In the 17 surviving rats, skin tumors (subsequently classified as ZyniDal gland tumors) developed in all, lung tumors (predominantly ade nocarcinomas) developed in seven, and osteochondromas developed in five rats. No tumors were observed in the 25 untreated control animals killed at an unstated tioe.1 Hale and female adult Sprague-Dawley rats were exposed by inha lation to concentrations of 10,000, 6,000, 2,500, 500, 250, or 50 ppm oi vinyl chloride for four hours daily, five days per week, for 52 weeks. Iha rats were found to exhibit the incidence of tumors shown in Table 10. There is evidence for the carcinogenicity of vinyl chloride in rats following prenatal exposure. Pregnant female rats (Sprague-Dawley) were exposed by inhalation to 6,000 to 10,000 ppm of vinyl chloride for four hours daily, between the 12th and 16th days of pregnancy. A single suocutaneous angiosarcoma was observed in the offspring of each exposure group at 75 weeks after the strrt of th? experiment.1>3 This indicates that vinyl chloride or metabolic conversion products traverse the pla cental barrier. There is evidence that vinyl chloride is carcinogenic via the gastrointestinal tract.^ Vinyl chloride dissolved in olive oil was ad ministered five times per weekto 320 13-week old rats in four groups (40 males and 40 females) in concentrations equivalentto 50.0, 16.6 and 3.3 mg/kg body weight. After 50 weeks, one angiosarcoma of the liver was observed in one male animal in the group given 16.6 mg/kg. This is equi valent to 663 mg total over a 52-week period. One angiosarcoma of the thymus gland was observed in afemale animal receiving 50 mg/kg, which is equivalent to three times that given the male animal. This oral dosage is equivalent to the total inhalational dose that induced both liver an giosarcomas and renal nephroblastoma, i.e., 800 mg.-* hamsters Preliminary results from inhalational studies in hamsters sug gest the carcinogenicity of vinyl chloride in this species3 (Table 11). A total of 266 male golden hamsters received vinyl chloride at various 42 BFG17064 21910049 INCIDENCES OF TUMORS IN- RATS EXPOSED TO VINYL CHLORIDE FOR 52 WEEKS AND SURVIVING UP TO 130 WEEKS 0c0ou>> vfut) 01 06 u ft) o. V0uwO9)) 43 BFG17065 21910050 C INCIDENCES OF TUMORS IN HAMSTERS EXPOSED TO V I L CHLORIDE .. FOR 28 WEEKS Xa pN pH o ^H o R CO 1 o oHE xo: 0> pe4 H U H JC M pH wXCOr Q. 0) pH o o o c 1 OH <0 EO XM0) w 0) CO oo c u w> U-i > pH o o < CO o ooo CO CO u .* o V- V > PH 40J) V 9 ^OH' pH CM O' pa CM 00 p-H PCMA a> > u cm CO 00 3 cm W <-h uh CO CO XuJ CO <0 4J o HE M CO PlAA CM pa pa <a pa pa CM PA PA CA A* 0 H cCO M CO CO e o ^ CO H M E fi. C>O <0 U 4J WCL TJ m X a> cx 9 0) o e u > 0) e> oo om o o o* 4A oM vd CM ioon CoA CM 1oA pCpO4 Moi* ueo 0 *M pH O o 60 W4-M1 -CuoO pH CO VeMM Uo4 M01 TJ 1 CoM CO < a* PA 0Oc) CWaM>l 006) 4hncaoJi Xu tVuOu9n 44 BFG17066 21910051 C\ ' ' concentrations for 30 weeks. The results after 28 weeks of exposure are presented in Table 11. In a second inhalational study in hamsters still in progress, a total of 200 Golden Syrians were exposed to either 2,500, 200, 50 or 0 ppa of vinyl chloride vapor seven hours per day, five days per week for 12 months. After only eight months of treatment, one liver angiosarcoma was observed in a male hamster exposed at 2,500 ppm. Control data were not adequately reported.2 Epidemiology and Case Reports In this section, information on the association between exposure to vinyl chloride monomer and the occurrence of cancer in humans is critically reviewed. Three types of studies have yielded this information: Case Reports--reports of clinical experience, with anecdotal opin ions on the relationship of some cancers to vinyl chloride. Cohort Studies--epidemiologic investigations designed to de termine whether vinyl chloride workers die of cancer at a higher than expected rate. ' * Community Stnd*.e<>- -tpiCwmiologic invusligations which search for elevated cancer mortality rates among dwellers in communities where there is known to be a potential for occupational and community exposure to vinyl chloride--that is, in commun ities in which a vinyl chloride facility is located. The evidence that vinyl chloride causes angiosarcoma of the liver in humans may be considered conclusive. There is strong evidence impli cating the chemical as a cause of cancer of the central nervous system, especially glioblastoma multiforme. The evidence for cancer of the lung and lymphatic system is suggestive but not cunciusivd. For other liver and biliary cancers, the evidence is weak. The evidence that vinyl chlo ride exposure is a cause of the buccal cavity and pharynx is too weak to be considered important. Case Reports In January 1974, Creech and Johnson reported three cases of angiosarcoma* of the liver in workers employed in a polyvinyl chloride *Angiosarcoma is tuu*. l ccaipo*eu of neoplastic endothelial cells. It is also known by the synonyms hemangiosarcoma and malignant hemangioendothelioma. The tumor may originate in organs other than the liver, although to the time of this writing, all reported vinyl-chloride- associated angiosarcomas appear to have originated in the liver. 45 BFG17067 ZS00T6TZ (PVC) polymerization plant in Louisville, Kentucky.5 This type of tumor was known to be extremely rare, appearing at a rate of only 0.05-0.2 new cases per million population^ (25 to 30 new cases reported in the U.S. annually).7 Thus, it became immediately apparent that this cluster of cases was unlikely to be a result of chance, and further studies were undertaken by these and other authors. As a result of these studies, which included investigations of other groups of vinyl chloride workers as well as experimental exposure to laboratory animals, vinyl chloride was strongly implicated as an agent capable of causing angiosarcoma of the liver in both man and animal. By December 1975, 45 cases of angiosarcoma of the liver had been discovered throughout the world,8 some in individuals living and some among the rec ords of the deceased. All had documented occupational exposure to vinyl chloride. The possibility that other ingredients or contaminants associ ated with PVC production were the cause of the tumors was rejected because none of these materials was present in other than minute concentrations compared to vinyl chloride itself, and none appeared to be capable of in ducing angiosarcoma in experimental animals. Also, a detailed investiga tion of some of the earlier reported U.S. cases revealed no significant exposure to substances known to be toxic to the liver,7 particularly the two types of compounds historically recognized to be capable of inducing angiosarcoma of the liver in humans--thorium dioxide (Thoratrast)9 and arsenic compounds.10 \ Further investigations established that exposure to vinyl chloride during the polymerization process was but one of several tvpes of exposure thaL could lead to the induction of angiosarcoma. For example, several cases wer,= reported in worxers involved in the production of vinyl chloride itself and two in workers engaged in fabricating PVC into the vast array of products for which it is used.H All evidence presently available indicates that these latter cases were attributable to exposure to residual unreacted vinyl chloride released from the PVC during fabrication, not to the PVC itself--there is no evidence to im plicate PVC as a cancer hazard. There have been reports of angiosarcoma of the liver occuring in individuals who, although not occupationally exposed to vinyl chloride, resided near a vinyl chloride facility--a fabrication plant in one casel2 and a polymerization plant in another.13 There have also been reports of cases of carcinoma of the liver (not angiosarcoma) in individuals occupa tionally exposed to vinyl chloride,14 in people living in the neighborhood of a vinyl chloride plant,15 and among family members of vinyl chloride workers.^ It should be emphasized that these reports in themselves are not sufficient to imply a definite causal relationship. 46 BFG17068 21910053 Cohort Studies The purpose of e cohort study is to compare the mortality pat' terns (incidence of the disease, death rate, and cause of death) of one group of individuals with another. The seven cohort mortality studies described here compare the mortality patterns of certain groups of vinyl chloride workers with U.S. population figures. Table 12 summarizes the major features of these seven cohort mortality studies. Ideally, a cohort study of vinyl chloride workers should: 1. Include information on a large number of exposed workers so that the presence of a relatively rare cancer can be detected, and to minimize the possi bility that by chance alone a cause of death will appear with an unusually high frequency; and 2. Identify all, or virtually all, of those workers exposed to vinyl chloride for a substantial period of time, preferably 10 to 20 years. None of the studies discussed here fully meet both of these desirable characteristics, but several come close, and the study findings are sufficient to indict vjr*vi rMf'--M.- -- 'r. c-.oabl" of <*:>> ?.g angiosarcoma of tpe liver in man Tabershaw & Gaffey 17,18--Manufacturing Chemists Association Study This study examined the records of 9,677 workers in 37 vi nyl chloride and PVC plants and compared their mortality experience with U.S. population figures. Only workers who by the end of 1972 had experi enced at least one year of exposure to vinyl chloride were included in Che study. In all, 707 deaths were known to have occurred in this cohort. An excess of deaths from cancer of the digestive organs and peritoneum was found, which was entirely explained by angiosarcoma of the liver. Also identified was an increased risk of developing cancer of the respi ratory system among exposed workers. This risk increased slightly with increasing intensity and duration of exposure. The death rate from lym phoma followed a similar but store pronounced pattern, the rate store than doubling in the group of workers with the highest intensity and longest duration of exposure. There was no increased risk found for leukemia. A two-fold excess in the number of deaths from cancer of the central nervous system was found and was statistically signifi cant. However, the excess was not related to duration or estimated Intensity of exposure to vinyl chloride. 21910054 47 BFG17069 1 um * i s c * a e | e .25-15* > t i S5 5 to M to ^liir;to * 1 > c ^Cto lit i 8 o e V6 8 i % i: dI e i to -- toi * to C c toto e ttoo t*o. s Ls; ?r !r`J; ill ill i.= * ti c9 W a 8* i s 48 BFG17070 N h> (0 K Oo Uc/1i Finally, a slightly increased risk of cancer of the buccal cavity and pharynx was found in workers with the lowest intensity and shortest duration of exposure t-*- vinyl chloride. This led the authors to suggest that this finding was likely to be the result of chance rather than a consequence of vinyl chloride exposure. Other studies nave not found an increased risk among vinyl chloride workers to cancers of this category. The findings reported in this study are enhanced in impor tance by the large size of the cohort and the very high percentage of the members of the cohort accounted for (95Z). Also, an important aspect of the study was the inclusion of an estimated exposure index. This index, although likely to be inconsistent somewhat from plant to plant and from year to year because it was necessarily based on subjective estimates ratner than actual air sampling, permitted some notion of the effects of duration and intensity to be included in the data analysis. Monson, et al!9--B. F. Goodrich Study This proportional mortality study was an analysis of 161 deaths occurring between 1947 and 1963 among B. F. Goodrich employees who had worked in either the company's vinyl chloride plant or in its pvc pr/*?!"er':T3tion plant. cl r'lent a were ia Iwr.cix k} . The percentage of deaths attributable lu various cancers ana other causes was calculated and compared with U.S. population figures. It was found that a higher-than-expected percentage of the 5. F. Goodrich workers had died from cancer of the liver and biliary tract. (This excess persisted even after subtracting all known cases of angiosarcoma of tne liver from the analysis.) A four-fold increase in the percentage of workers who had died of cancer of the brain was found, as was a 50X increase in cancer of tne lung. Cancer of the lymphatic and hematopoietic system also showed a 50a increase. Altnougn it must be emphasized that proportional mortality studies such as this do not express the risk of developing cancer or any other disease, the complete ascertainment of cause of death in active and retired employees over the entire study interval was a major strength of tnis study. Aspects of the study which tend to weaken the significance of the positive findings are: (1) no information was obtained on living workers who had left B. F. Goodrich employment before retirement; (2) no information was obtained on intensity or duration of exposure; and (3) many persons were apparently included in the study who had never been exposed to vinyl chloride. 0 21910056 49 BFG11071 Nicholson, et al^l--Goodyear Study The population studied was 257 individuals, each with a history of at least five years of exposure to vinyl chloride in a PVC polymerization plant during the period 1946 to 1963. In each case, 10 or more years had passed since commencement of employment. Twenty-four deaths were identified, including three con firmed cases of angiosarcoma of the liver, one brain cancer, and two lym phomas. The authors suggested that a causal relationship between vinyl chloride exposure and the appearance of these relatively rare cancers was likely. A major achievement was that 255 out of 257 (99Z) members of the cohort were successfully located and their current health status determined. The requirement for over five years of exposure was also important in that it increased the likelihood that any given member of the cohort had a reasonable degree of contact with vinyl chloride. The absence of air sampling data and the availability for analysis of only 24 deaths, limit the extent to which the findings of this study can be considered representative of the true mortality patterns for workers in PVC polymerization plants. Ott, et al22 and Holder^--Dow Study The population in this study was 594 chemical workers ex posed to vinyl chicTids st & single vinyl chloride aar.vf scturiiig Ijcliity between the years 1942 and 1960. Expected deaths in thin study were de termined from U.S. white'male mortality rater. Eighty-rsight individuals were known to have died; death certificates were located for 86 of tnese. An exposure rating of low, intermediate or high, depending upon existing industrial hygiene data, was assigned to each member of the cohort. The authors of the study concluded that workers exposed to vinyl chloride at levels in excess of 220 ppm experienced an "apparent in crease in overall malignancy rate." However, this increase was not found to be statistically significant. Angiosarcomas of the liver were not found at any level of exposure. The value of this study is enhanced by the availability of air-sampling data specific for vinyl chloride exposure as well as by a successful followup of over 95Z of the cohort. Some misclassification of dose-response relationship is apparent, and to some extent this con fuses the study results. For example, in order to cope with the fact that many employees had been exposed to a rather wide variety of concentrations of vinyl chloride at different times during their employment, the authors assigned each employee to the exposure group representing the highest level of exposure that he or she had experienced for more than one month. Then, in assessing duration of exposure, the authors only considered du ration at the highest level to which the employee had been exposed. As a result, a worker whs, for example, had spent two months at the highest 50 BFG17072 21910057 ( exposure level and 20 years at the intermediate exposure level, is clas sified as "high exposure--less than one year," even though, of course, his exposure had been of much longer duration. Because of this method, an unknown proportion ot employees are misclassified by duration. The ex tent of this misclassification may be sufficient to explain the lack of observed risk gradient with increased duration of exposure. A major confounding variable in this study was that 72 of the workers included were also exposed to arsenicals, which themselves are known carcinogens. Therefore, it was necessary to reduce the study population from 594 to 522, a requirement recognized by the authors and, accordingly, incorporated in the analysis. Of these 522, 228 had less than one year of exposure and may not have been truly part of the popula tion at risk. Ninety-eight of these workers had ten or more years of ex posure, and 34 were exposed for a minimum of 20 years. The authors did not analyze these groups separately; rather they reported the cancer risk of all workers with one or more years of exposure. Separate analysis of the data from workers with longer exposure would have been helpful to the interpretation of the study results. Duck, et al^4--British Petroleum Study This study included 2 12n male employees exposed to vivv; chl.or.iUc: a ywi>iic.izction .n Wales during the period 1948 to October 1973. Until 1968, vinyl chloride was also produced in this plant. The authors compared the mortality experience in the exposed popu lation with that experienced by males ages less than 75 years in England and Wales, 1955-1972. They found no excess of cancer deaths overall, nor was an increase in deaths from cancer of any specific site observed. This study has several major strengths. First, only seven of 2,120 subjects were lost to followup and, secondly, many of the partic ipants had long exposure periods--582 had 10 or more years exposure, and 336 had 15 years or more. Weaknesses of cite' study include the absence of information on air concentrations, which precluded the inclusion of expo sure intensity in the analyses. Moreover, the authors were unable to re alistically separate jobs by intensity or duration of exposure. 21910058 Waxweiler et al25--National Institute for Occupational Safety and Health (NIOSH^ and Center for Disease Control tdDCj Study m This study by the NIOSH and CDC included 1,294 workers em ployed in four PVC polymerization plants. Each study subject had five or more years of exposure, and, for each, a period of ten years had elapsed since the date cf flirt xousure. 7>t addition to the cohort study, all deaths from cancer of any site, or liver disease of any type, recorded on a death certificate were investigated further, regardless of whether the case met the cohort-inclusion criteria of five years exposure and ten years latency. 51 BFG17073 Of che 14 histologically confirmed cases of biliary and liver cancer among workers from che four plants, 11 cases of angiosarcoma were found, all of which were in workers who had worked as reactor clean ers. The authors also identified a three- to five-fold increased risk of cancer of the central nervous system (3 cases). In 9 of 10 brain cancer cases that included 7 noncvhcrt errs**. ' liigr.osis glioblastoma multi forme was made. (No histological diagnosis was available for the tenth case.) The authors compared this finding with the results of an autopsy series reported by Manuelidis and Solitaire^ in which only about one-third of the tumors of the central nervous system were found to be glioblastoma multiforme. The authors also found a 50% increase in risk for respiratory system cancers and for cancers of the lymphatic and hematopoietic system. This study has a number of major strong points: (1) the authors were able to locate greater than 99Z of the cohort, and (2) the population of the study was not significantly diluted by minimally ex posed individuals. Also, the study compared the findings for one plant-- which contributed more than two-thirds of the total person-years of ex posure--with the population of three other plants. Similar results were found in each of the two groups, suggesting that the excess risks observed were not peculiar to a specific plant, but rather resulted from vinyl chloride exposure. Data on air concentrations of vinyl chloride were not avail able; therefore, dose-response relationships could not be examined. Pasternack-* -yircfctone atedy TI.I* iitudy examined all 85 ciu'-.' occurring between 1947 and 1974 among active and retired employees of a chemical and plastic plant complex. According to the author, employees in these 2 plants were all exposed to vinyl chloride and were the only employees in the complex so exposed. In addition, the mortality experi ence of 348 tire-plant workers, unexposed to vinyl chloride, was examined for comparison. Utilizing information obtained from death certificates, .. the author compared the proportion of the 85 deaths, by cause, with the proportion of U.S. white male deaths, by cause, during 1968. He also compared the proportion of deaths, by cause, between the 85 vinyl chlo ride workers and the 348 tire-plant workers. One death from angiosarcoma of the liver and one death from brain cancer were found. A slight excess of cancers of the respiratory and digestive system was present in both groups when compared with the U.S. white male population figures. However, there was no significant excess in deaths from any specific cancer when the mortality experience of the 85 vinyl chloride workers was compared with that of the 348 tire-plant workers. Like the Monson, et all9--g. p# Goodrich study, this study accounted for every death in active and retired employeea, a definite strength. A confusing factor, however, is the choice of tire-plant 52 21310059 BFG17074 workers for comparison since tire workers are thought to be at increased risk of cancer development themselves. Community Studies Aspects of a study of the distribution of birth defects in residents living in three Ohio communities,28 where vinyl chloride production facilities are either located or are nearby, are reported elsewhere in Chapter 111. For the purpose of this section, however, the cancer mor tality data reported in this study are relevant. Thirty-eight deaths from tumors of the central nervous system were reported among the residents of these communities during the period 1958 to 1973 in whites aged 45 and older. Based on the rates for Ohio, only 24 deaths from cancer of this site would be expected. This differ ence is statistically significant (p < 0.01). This study has many important limitations. No information on ambient air levels of vinyl chloride was presented, nor is it known wnether the plants use vinyl chloride or FVC. Also, no consideration was given to ocher environmental factors that might contribute to the incidence of cancer, such as infectious agents, ocher industrial exposures, background radiation, genetic factors, or exposure to other chemicals, Personal basic tswcLi as sacking were not consj-dtieu. Dose-Response Relationships The existence of a dose-response relationship between exposure to vinyl chloride and development of angiosarcoma of the liver has often been suggested. Support for this notion is found in the observation that Che earliest reported victims of angiosarcoma all began their work in the industry as polymerization vessel cleaners, and were, in the course of that work, exposed to-extremely high concentrations of vinyl chloilue gas. Moreover, one research study? noted an inverse relationship between the length of time spent as a polymerization vessel cleaner and tne period between first exposure and tumor diagnosis. However, no information ap- - pears to be available on risk as a functionof time spent as a vessel cleaner, and this question was not examined in any of the studies reviewed here. Thus, while it is not known just how likely it is that a vessel cleaner will develop the tumor, it appears that if he is going to do so, the length of time he spent at that occupation will influence how quickly tne tumor will appear. m Several cohort studies were able to examine dose-response* re lationships, although in a relatively imprecise fashion. The Tabershaw and Gaffeyl7. 18 study found r dose-response relationship with intensity and duration of exposure in the case of several cancers. Listed in order from the strongest to the weakest relationship, these are: 21910060 53 BFG17075  Digestive system cancers (entirely explained by angio sarcoma of the liver). Cancers of "other and unspecified sites" (nearly one half of these cases were brain cancers). Lymphoma. Lung cancer. The Dow study had access to actual air-sampling data, but, because of the small number of individuals in the cohort, the study was of limited value as an indicator of dose-response relationships. The Duck, et al24 British Petroleum study found no gradient of response with duration of exposure for cancers of the digestive system or lung, nor in this study was there a gradient of response with duration of exposure for all cancer sites combined. Discussion Angiosarcoma of the Liver Because of the rarity of this tumor, the case reports al ready available clearly reflect the presence of a greatly increased risk among workers exposed to vinyl chloride gas. The fact that some of the cohort studies failed to detect this increase in risk is probably a re sult of misdiagnosis, a circumstance clearly verified by Tabershaw and Galley.1' These authors found that on death certificates, angiosarcomas of the liver had been diagnosed as liver carcinoma, or `.ven as cirrhosis. Other Liver and Biliary Cancer In the Waxweiler et al25--NIOSH and CDC study, an excess of liver and biliary cancers was found. Other studies either found no excess in this cancer category or found an excess that could be explained completely, by angiosarcoma of the liver. There have, been isolated case reports of cancer of these sites occurring in individuals with possible environmental exposure, such as neighborhood or household exposure; but because these tumors are not so rare as angiosarcoma of the liver, these findings must be considered as only suggestive. Central Nervous System Tumors Host studies have found a higher risk of these tumors in vinyl chloride workers than would be expected based on U.S. population figures, but the excess has not been related to duration or intensity of exposure. In those studies that did not find a higher risk, the failure to do so may be a consequence of small cohort size. Thus, it is sugges tive, but by no means conclusive, that vinyl chloride is a cause of cancer of this site, especially glioblastoma multiforme. 54 BFG17076 21910061 Lung Cancer Most studies have found an increased risk of cancers of this site among vinyl chloride workers in comparison with U.S. population figures. The failures of the Nicholson, et al.21--Goodyear and, perhaps, the Ott, et al.22 and Holder23--Dow studies to find an increased risk in this category could be due to the small cohort size. There is no clear explanation for the failure to find an increased lung cancer risk in the Duck, et al.24--British Petroleum study, other than the possibility that no increased risk of lung cancer truly exists in vinyl chloride workers. Thus, the evidence that vinyl chloride causes lung cancer is suggestive, but far from conclusive. Cancer of the Lymphatic and Hematopoietic Systems Most studies show an increased risk of cancer in these cate gories. The Tabershaw and Gaffeyl?> 18 study suggests that the increased risk is for lymphoma, rather than leukemia. Again, the failure to find an increased risk in this category by the Ott et al.22 and Holder23--Dow study may be the result of small numbers. The negative findings of the Duck, et al.24--British Petroleum study are unlikely to be explained by methodological problems; thus, they must be considered inconsistent with the findings of the other studies. Accordingly, It can only be said that the increased risk of cancer in these categories among vinyl chloride workers is suggestive--not conclusive. Cancer of the Buccal Cavity and Pharynx The Tabershaw and Gaffeyl?, 18 study identified increased risk for this site, but only in those groups with the lowest level of ex posure and the shortest duration of exposure. No increased risk of cancer of this sice was found in any other study, and the authors themselves noted that this finding is unlikely to be due to vinyl chloride exposure. 55 BFG17077 Z900T6T2 Chapter V CANCER CONTROL PROGRAM FOR EXPOSURE TO VINYL CHLORIDE Control of the health hazard associated with exposure to vinyl chlo ride depends largely upon reducing exposure in the workplace and in the general environment, and this, in turn, depends principally on application of appropriate engineering control measures. Also important in control ling this health hazard are two other measures--medical surveillance and education. These three control measures are the subject of this chapter. Engineering Control Substantial progress has already been made in reducing exposure to vinyl chloride both in the workplace and in the general environment. Ef fective engineering control is a demonstrated reality in many vinyl chlo ride facilities, and the technology exists to extend satisfactory control to almost all monomer production plants and PVC manufacturing facilities. Since these sites are the source of about 962 of all vinyl chloride emitted into the nation's atmosphere (see Chapter II), it is of paramount impor tance that they be considered a primary target for control. Ihia section is not intended as a aeiailed-process design manual, but as a guide to essential elements of good engineering control practice that will permit informed community review of a total control program. The specific measures to be taken at each site must be dictated in large part by the nature of the process and by the professional judgment of the con trol engineers responsible for implementation of the control strategy. Simplified schematic flow charts of some of the major steps in the vinyl chloride-PVC-fabrication chain are given in Figures 5, 6, and 7. Areas wnere experience has shown th*t major emissions are likely to occur are indicated. Monitoring for Vinyl Chloride Exposure The principal goals of a vinyl chloride monitoring program are to identify and prevent excessive exposures, whether in the workplace or the general environment. The selection of times and places where monitoring should be undertaken and the selection of appropriate methods require knowledge of the processes in operation as well as the statistical, physical, and chem ical bases of the monitoring method. The aim of the monitoring program should be clearly defined, and assistance should be sought from process 57 BFG17078 21910063 ( ?9 R ecycle HCV 219 r CO O 59 O BFG17080 0> U\ ( 60 , BFG17081 99QOT6TZ engineers and regulatory agency representatives in the design of the pro gram. (Agencies that can provide assistance are listed in Appendix E.) Additional goals of the monitoring program may include evalua tion of effectiveness of control methods and definition of exposure for epidemiologic studies. Several chapters in the NIOSH training syllabus, "The Industrial Environment: Its Evaluation and Control,"! offer valuable guidance on the general monitoring principles applicable to both occupa tional and general environments. Determination of compliance with appro priate standards may be accomplished through application of methods found in two other NIOSH publications: "Handbook of Statistical Tests for Eval uating Employee Exposure to Air Contaminants"2 and "Statistical Methods for the Determination of Noncompliance with Occupational Health Stand ards."3 More generally useful statistical techniques are available in the National Bureau of Standards publication "Experimental Statistics."^ The Occupational Environment Two major vinyl chloride monitoring strategies have been applied successfully in programs for control of the occupational environ ment. Strategy One is the most common and involves collection of samples followed by a separate analytical procedure. Strategy Two relies upon the use of direct reading or continuous monitoring instnunesiL*" TM Strategy One involves the application of one of two differ ent sample collection techniques. The first of these techniques is con tained in the NIOSH Manual of Analytical Methods, 1974? and is referenced in the OSHA vinyl chloride exposure standard of 1974 as meeting the OSHArequired standards for accuracy. In this method, a known volume of air from the worker's breathing zone is drawn through an activated charcoal tuoe with the aid of a small pump. The trapped vinyl chloride is then desorbed with carbon disulfide, and an aliquot is injected into a gas chromatograph for analysis. Several modifications of this method have een published.3,- In the second sample collection technique, the breath ing zone air is collected in an aluminized gas sampling bag without con centration^ and then analyzed directly by gas chromatography. With either sampling method, sample collection should be planned so that evaluation of both Time Weighted Average (TWA) and 15-minute exposures is possible. The recent development of a monitoring "badge" which does not require the use of a pump for sample collection has been reported. The advantages of Strategy One are that it may be readily adapted to monitoring individual exposures and that airborne concentra tions may be determined with considerable accuracy. Its disadvantages include: (1) the requirement for a skilled chemical analyst; (2) the lag time between sampling and receipt of analytical results (potentially re sulting-in a delay in anplic-2-tion of control measures); -and (2) measure ments are necessarily intermittent and thus may not identify peak concen tration periods. 61 BFG17082 21910067 The direct reading instruments with which to implement monitoring Strategy Two may be either portable, or may be fixed (nonpor table) with probes that extend to work areas to be sampled. Continuous monitoring instruments are nearly always fixed with information output recorded in permanent records; the only external indication of activity being an alarm system set to respond to a predetermined vinyl chloride air concentration. The advantage of direct reading and continuous monitoring instrumentation is that an immediate indication of airborne concentration is provided. In addition, continuous monitoring systems have the capabil ity to monitor many areas in closely successive time periods, utilizing a "switching" network of valves and sampling probes, thus providing the flexibility to immediately modify processes when vinyl chloride concen trations are found to be excessive. The disadvantages of this approach include high initial cost, rigidity of installation where systems are fixed, and difficulty in relating measured concentrations to individual exposures. An effective monitoring system should utilize the best of both strategies to maximize benefits. For example, personal samples may be taken in the breathing zones of workers, while a fixed, continuous mon itoring system may be utilized to warn of leaks and to call immediate at tention to areas where concentrations are excessive, and hand-carried, direct reading monitors are used to survey plant or process emissions. Table 13 summarizes the advantages and disadvantages of these two monitor ing strategies. t -t Even the most vigorous efforts to reduce vinyl chloride air concentrations to desired lv;vc'r may -ot v-ways bo fully successful It is therefore advisable to warn employees when concentrations rise above recommended limits. Continuous monitoring of in-plant air should be car ried on with a detecting device equipped to trigger a preliminary alarm at 1.0 ppm, and a warning to immediately don respirators at 5.0 ppm. A properly calibrated, nonspecific flame ionization detector or an infrared spectrophotometer is most often used for this purpose. The usual back ground level of other hydrocarbons can be partially accounted for in the calibration so that the results will generally reflect only vinyl chloride concentrations. More sophisticated systems using gas chromatographic col umns specific for vinyl chloride are preferable and are now readily available. Several systems, using either flame ionization or infrared are now available from commercial vendors. Most installations are designed specifically for the characteristics of the facility where they are to be installed. An example of the successful application of this concept is the system at Pantasote Corporation in New Jersey, which is described in Appendix C. In addition to its use in protection of individual workers, such a system may have inlets situated at points where emissions may be expected and thus aid- in early detection and correction of leaks. 21910068 62 BFG17083 Table 13 ADVANTAGES AND DISADVANTAGES OF MAJOR MONITORING STRATEGIES Sample collection fol lowed by separate ana lytical procedure Advantages Disadvantages Airborne concentrations may be determined with considerable accuracy May be adapted to mon itoring individual ex posures Requires a skilled chem ical analyst Time lag between samp ling and reported re sults Difficult to obtain measurement of high peak concentrations Direct reading instru mentation Immediate indication of concentrations Imprecise and subject to interferences Flexibility to modify processes immediately wn-.-n concentrations arr found to be excessive Maintenance and opera tional cost? are high Continuous monitoring - Capability to monitor many areas in closely successive time periods High initial cost Rigidity of fixedsystem installations Difficult to relate concentrations to in- . dividual exposures Source: SRI 21910069 63 BFG17084 The General Environment The EPA national emission standard for vinyl chloride con tains a test method procedure to determine compliance. Samples of stack gas (or ambient air) are to be collected in Tedlar** or aluminized Mylar* bags. Water or waste sludge samples are to be collected in glass vials with Teflon* cap liners, Ambient .air samples nave also been successfully collected by drawing air through charcoal adsorbent tubes for a 24-hour period.9 The analysis of vinyl chloride content in PVC products or foods requires specialized solution techniques for sampling.10 Ethanol and n-heptane are used as solvents to simulate the action of alcoholic and fatty foods, respectively.il These food categories have been shorn to have the greatest potential for leaching vinyl chloride from rigid or semirigid PVC products. A recently reported method simplifies the food and polymer sampling procedure and provides an analytical method that is useful for the detection of vinyl chloride in foods with a minimum detect able concentration of 50 parts per billion (ppb).12 Analysis All analytical methods currently acceptable to federal regulatory agencies are based on the use of gas-liquid chromatography with a flame ionization detector. ' The OSHA standard requires that methods of sampling nd analysis lor viv.yl chloride have a lower detectable limit of o.?s ppm with precision at the 952 confidence level of 502.13 The EPA requires equivalence lc me meL'.iods given in detail in its standard with no stated precision or sensitivity.14 A skilled analytical chemist with modern la boratory facilities will be able to detect concentrations of a few ppb in air if adequate sampling methods are employed. The FDA-referenced methodic is sensitive to 0.05 parts per million (ppm) vinyl chloride in foods and 1.0 ppm in PVC, while other methods permit detection of as little as 10 ppb in vinegars and alcoholic beverages. 15 Control Measures for Emission Sources Polymerization Plants In PVC facilities, the primary sources of emissions requir ing application of control procedures include: Opening and cleaning of reactor vessel. Discharge of relief valve. m Piping joints. 64 21910070 BFG17085  Stripping process equipment. fugitive vinyl chloride sources--dryers, bulk storage, blenders, pumps, and valves. Control will generally embody the use of some or all of the following measures. Process or Procedure Change--Many of the measures that have been taken to reduce occupational exposures and emissions to the community have involved changes in the processes used in handling vinyl chloride and PVC. Some examples are: Using high-pressure water or steam to clean poly merization reactors remotely, rather than the old practice of sending workers into the reactors for manual cleaning. Lengthening the reaction time of polymerization so that the amount of monomer entrapped in the PVC is minimized. Inserting rupture disks upstream of relief valves to reduce leaks. Using exhaust hoods with filters in laboratories where samples of vinyl chloride are prepared for analysis. Using closed-loop vapor return systems at loading and transfer stations. Substituting closed gauges for open-end slip gauges to measure the contents of a tank car. Adding vacuum or steam stripping steps at the end of polymerization to reduce the vinyl chloride con tent of PVC. Maintenance and Surveillance--Because vinyl chloride is colorless and odorless at hazardous concentrations and is under pressure at all stages of transfer, storage, and polymerization, a program of con stant vigilance and maintenance of all possible sources of leakage must be carefully followed. Local Exhaust Ventilation--A local exhaust ventilation system designed so that released vii.yi v.nloriae is immediately captured and removed from the ambient air will add to the effectiveness of any con trol system. This has been particularly effective in reducing emissions from tank car transfer operations. Ventilating systems may be designed 65 BFG17086 21910071 to actuate when excessive levels of vinyl chloride are detected at some point in the plant by a continuous monitoring system. Gas Cleaning--All gases collected by the exhaust ventila tion system or vented by relief valves must be cleansed so that no more than 10 ppm of vinyl chloride remains in the emission gases (dilution with additional air is not an acceptable method to reach the 10 ppm con centration). There are three types of emission controls that EPA consid ers to be technically and economically feasible for this purpose: acti vated carbon adsorbtion, solvent extraction, and incineration. Conventional heat exchangers may be used as a preliminary step to reduce the vinyl chloride content of the gas stream, although they are not very efficient because of the high vapor pressure of the vinyl chloride monomer. Carbon adsorption and solvent extraction offer the potential advantage of recycling the collected monomers. There is a possibility of polymerization of the adsorbed monomer on the surface of tne carbon, which might lead to rapid loss of adsorption capacity. Although incineration is probably the most thoroughly tested and immediately feasible of the three types of emission control, it does have economic disadvantages including: loss of monomer, need for fuel to support combustion, and rapid corrosion of incinerator components from HC1 formed during combustion. Too few data are available tc completely assess the actual or potential effectiveness of any of these systems in any operation, and it is suggested that the regional. EPA office be consulted fct u^plicable standards and recent assessment of currently available technology. Other Measures--The control of monomer content in PVC should include treatment of waste sludge discharged from incomplete poly merization reactions. Where the vinyl chloride content cannot be effec tively reduced, the waste should be disposed of in such a way that human contact is minimized, with attention given to landfill operators, refuse collectors, and others who may be exposed to the waste. The potential for release of vinyl chloride during inefficient combustion of PVC at low temperatures must be recognized if incineration is chosen as the means of disposal.16 Significant quantities of vinyl chloride may be released from relief valves if a reaction does not proceed properly and excessive pressure builds up in the reactor.17 There is a significant risk of ex plosion in this event, and release to a larger vessel or to the atmosphere is essential. Appropriate piping and gas cleaning capability must be provided in anticipation for this emergency so that the discharged gas stream is reduced to 10 ppm. Preparation for recharging the reactor vessel after comple tion of polymerization must employ several emission control procedures. 66 BFG17087 21910072 In addition, the following biochemical tests are to be done: total bilirubin, alkaline phosphatase, serum glutamic oxaloacetic trans aminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and gamma glutamyl transpeptidase (GGTP). If abnormalities are found, the standards require that these tests be repeated. If tests remain abnormal, consider ation must be given to withdrawal of the employee from contact with vinyl chloride while a more comprehensive medical examination is made. Accord ing to these regulations, examinations should be performed every six months on individuals who have been employed in vinyl chloride or PVC manufactur ing for ten years or longer and annually for all other employees. The standards require the employer to obtain a statement of each employee's suitability for continued exposure to vinyl chloride from the examining physician promptly after examination, and to provide a copy of the statement to the employee. Withdrawal of the employee from possible contact with vinyl chloride is required if continued exposure would mate rially impair health. A Medical Surveillance Program--Louisville. Ky. Tamburro and his associates have reported their experience,22-24 in developing a medical surveillance program for vinyl chloride workers ir Louisville, Kentucky. Each participant in the program receives an .;.i.:.','l essmincif. jii ....c periodic examiudL ions: i The initial examination of each participant in the pro gram consists of a personal and occupational history, a general physical examination, a chest roentgenogram, and the following laboratory determinations: complete blood count (CBC), urinalysis, SGOT, SGPT, total biliru bin, alkaline phosphatase, and GGTP. Tamburro and his colleagues feel that the initial examination should also include a functional test of liver clearance, of which there are a number available. Among theso are indocyanine green (ICG), sulfobromophthalein (BSP) and bile acid, radiobilirubin, or aminoacid clearance.24 Periodic examinations are done at least annually on all participants and at six-month intervals on individuals exposed to vinyl chloride at the OSHA "action level" (an airborne concentration of vinyl chloride of 0.5 ppm av eraged over an eight-hour work day)26 and at six-month intervals on certain employees known to have had high exposures in the past. This periodic examination in cludes a chest roentgenogram and laboratory determina-. tions identical to those performed during the initial examination. In addition, a radioisotopic liver-spieen scintiscan is included to detect possible de formities in the liver, spleen, or both. The results of 71 BFG17092 21910077 each participant's examination are assessed by the re sponsible physician and a decision is made with regard to the need for repeat or additional tests or special procedures. A similar medical surveillance program has been described by investigators in the United Kingdom.25 Tamburro and his associates also have given considerable atten tion to an aspect of medical surveillance that has historically received little or no consideration--the creation of an active data bank. In this computerized bank are all available clinical, biomedical, radiologi cal, and physiological study data for each surveillance program partici pant. Work is under way to add various estimates of intensity and duration of exposure such as job classification code, employee work history, and chemical exposure history.27 With these data, an index of exposure to any of several chemi cals can be calculated by which the average and total exposure of any in dividual or group can be realistically estimated. Computerized printouts of biomedical and exposure information have been designed and utilized for a variety of purposes such as communication of test results to the private physicians of individual employees. The data bank also includes provisions for an early warning system and epidemiological programs.27 Educational Control It is iiot sufficieuc for purposes of control that a carcinogenic suDstuiice !; identified, that standards are promulgated regulating its manufacture and use, and that control measures are taken to eliminate or limit the physical contact between the substance and humans. It is also necessary that methods be developed to educate and thereby modify tne behavior of those persons who interface with hazardous substances. However, given the paucity of information on the effectiveness of educa tional programs dealing with hazardous substances, it is difficult to de termine whether behavioral modification would be best accomplished through use of formalized educational programs or of more psychologically oriented techniques. A succinct definition of the goal of public education regarding cancer has been given elsewhere--i.e., to: Educate the public about treatable forms of the disease Motivate individuals, especially those at high risk, to participate in screening programs designed to detect early forms of cancer Persuade those with recognizable signs or symptoms of ill health to seek early medical advice.28 72 BFG17093 21910078 This goal is consonant with the goals of the National Cancer Institute's National Cancer Plan, and it is in this context that the educational aspects of a control program for vinyl chloride-induced disease are pre sented here. Discussed in the following paragraphs on educational control are: OSHA regulations and education; the understanding of "risk;" results of an important National Academy of Sciences study of cancer education; and, finally, some information resources that could prove helpful to anyone concerned with the educational aspects of cancer control. OSHA Regulations--Education In those situations where a chemical substance is regulated by government agencies as a carcinogen, an educational process has already begun through promulgation of regulatory controls. Moreover, the 1974 OSHA regulatory standard for vinyl chloride mandates employee training concerning the health hazards of exposure to the substance including, specifically, the carcinogenic hazard. Employers subject to this regulation must ensure that employees receive initial and annual training concerning which operations could result in excessive exncrvre to -v. "M'lr-ci.-; the purpose, "repor use, ahd limitations of respiratory protective devices; the nature of a required environmental and personal monitoring program; the purpose and description of a required medical surveillance program; and conditions that could result in release of vinyl chloride. In addition, the employer is required to provide OSHA a copy of all training materials on request. It could be assumed, then, that the populations at highest risk of vinyl chlorideinduced disease are receiving the benefits of a mandatory education/training program througn their employers. Unfortunately, the beneficial effects of these mandatory training programs on the behavior of the employee have not been evaluated. How well such employees have grasped the significance of relative and individual risk should be a matter of great concern to those responsible for worker education. Understanding "Risk" Of the numerous aspects of cancer about which the worker should be informed--as enumerated in the following section of ttris chapter (see particularly Table 16)--one of the more important and complex is how. in formation should be evaluated and interpreted in terns of the risk that is present in the workplace. In the case of vinyl chloride-related angiosarcoma of the liver, a conceptual understanding of risk by the employee is complicated by the fact that there is an extremely high relative risk, which may approach 73 BFG17094 21910079 200 Co 400 times Chat of unexposed workers, but a very low actual or in dividual, risk. The average annual incidence of liver angiosarcoma in U.S. males is approximately 0.02/100,000. Given this incidence rate, the expected annual number of new cases of the disease among 7,000 vinylchloride-exposed workers--even if all were at highest relative risk (i.e., 400 times that expected)--would be less than 1. It could be assumed that the recent reduction in exposure con centrations effected by the 0SHA regulation would have the effect of greatly reducing the exceedingly high relative risk. But this assumption, in turn, would pertain principally to only those new workers who have benefited from the 500-fold reduction in the permissible exposure concen tration. These considerations can be extremely confusing to workers who simply wish to understand whether they risk insidious health hazards during the performance of their jobs.* A National Academy of Sciences Study Working under an interagency agreement with the National Cancer Institute, OSHA funded a program in 1975 to determine how best to inform workers concerning carcinogenic hazards in the workplace. Part of this program included a contract with the National Academy of Sciences (NAS) to form a select Committee on Public Information in the Prevention of Occupational Cancer. The work of this Committee was completed during 1977, and a report entitled "Informing Workers and Employers about Occupational Cancer" was published by the Academy.29 Inis report is of utmost importance to this monograph because it brings together a select groun of i.reeminent individuals possessing special expertise in fields of cancer biology, environmental medicine, communication, journalism, occupational medicine, epidemiology, lav, and oenavioral sciences. At a time when the methods used to inform workers of carcinogenic hazards are largely derived on a subjective basis, the recommendations of this Committee must be considered as the most appro priate available. Hence, pertinent sections of the Committee's report are reviewed here. Legal and Ethical Bases for Providing Information The NAS Committee concluded that both public law and pub lished standards clearly establish a requirement for training the employee with regard to the hazards of substances with which they work, and that current laws "clearly contain a legal basis" for providing public infor mation on the prevention of occupational cancer. None of this is to suggest, however, that vinyl chloride should not be avoided, if possible. 74 BFG17095 21910080 From Che standpoint of ethics, the Committee agreed that there is a fundamental ethical principle that may best be called the "right to know." The Committee said it believed that the readiness with which the Committee members accepted this principle "parallels the increas ing concern of society as a whole with the individual's right of selfdetermination." The Committee stated further that it believes it is "unethical and unrealistic" to (1) assume that the right to know requires employers to inform workers about only the few chemicals that nearly every one agrees are human carcinogens and (2) argue that the right to know requires only that sunmary information concerning the exposure of workers to suspected carcinogens "be made available for inspection"--it is neces sary for government agencies and employers to make reasonable efforts to ensure that workers comprehend the relevant material as well. The ethical test for whether particular information must be divulged, the Committee said, is whether it is relevant to the employee's decision. In this light, the Committee recommended that, in spite of the anxiety that is frequently associated with cancer hazards, information essential to the understanding of risk by the whole group of employees should not be withheld on the chance that it might cause anxiety in some. Target Audience end Information to be Conveyed The Committee felt that the most readily indentifiable target audience would be the unionized employee, with the most difficult target audiences being farmers and others engaged in agriculturally related activities such as migrant workers. Families of workers were also indicated as prime target audiences, and the Committee recommended chat programs be designed to reach such families. The Committee recommended that information concerning car cinogenic hazards in the workplace should: Provide sufficient awareness to permit job applicants to decide whether they would want to work in the face of the hazard or to allow present employees to decide whether they wish to continue work. Tell the employee how to take steps to minimize his own exposure. Be sufficient to permit the worker to assist to the limit of his capability in monitoring*and improving the environment of his workplace. The Committee went on to recommend specific items of infor mation that should be presented to employees and employers with regard to both (1) the hazard of occupational cancer in general, and (2) a specific substance once it has been determined that it is, in fact, a carcinogenic. These recommendations are presented in Tables 15 and 16. 75 BFG17096 21910081 Table 15 WHAT THE EMPLOYEE AND EMPLOYER SHOULD KNOW ABOUT OCCUPATIONAL CANCER IN GENERAL 1. Many carcinogenic substances can be absorbed by man without any warning signals such as coughing, burning, or nausea. 2. If permanent damage is doue to a cell by a carcinogenic agent, the defect is passed on to daughter cells in the presence of multiplicaton; the effects of repeated exposure can therefore be additive. Moreover, some agents are not readily eliminated from the body so their concentrations increase with repeated exposure. 3. There is usually a latent period of from 5 to 30 or more years between the first absorption of the carcinogen and the appearance of any sign of the disease. 4. Although there is still some debate within scientific circles, for all practical purposes there is o dose of a carcinogen below which one can say that there is absolutely no risk of it causing cancer. Nevertheless, decreasing the exposure decreases the risk and increasing it increases the risk. 5. The hazard of a carcinogen is in some iT'ctances multiplied if if is absorbed in conjunction with other substances, such ns cigarette smoke. 6. Some carcinogens can De inadvertently transferred fijra the work place to the home in significant quantities. 7. An indication that a substance may produce cancer in man is frequently found in experiments on laboratory animals and cells. When an agent is demonstrated in controlled experiments to produce cancer in animals, that agent should be regarded as possibly carcinogenic in man. 8. In some instances, benign tumors develop into cancer and, in many instances, agents that produce benign tumors increase the risk of cancer. Source: National Academy of Science (Chapter reference 29). 76 BFG17097 21910082 r Table 16 WHAT THE EMPLOYEE AND EMPLOYER SHOULD KNOW ABOUT A SPECIFIC CARCINOGENIC SUBSTANCE 1. The identification of the substance in question by the name used in the workplace and, where possible, by generic name. 2. Data on the carcinogenicity of the substance including evidence from human epidemiologic studies, animal studies, and other valid techniques. 3. An interpretation of the risks in the workplace implied by the above data. 4. Description of the disease in man, where applicable. 5. The route of exposure in the workplace. 6. Required and recommended measures to reduce exposure, including contaminant and disposal measures, monitoring procedures, and individual protective measures. Source: National Academy of Sciences (Chapter reference 29). 77 BFG17098 21910083 The Committee recommended that OSHA should take necessary steps to ensure that carcinogenic substances were readily identified, that lists of commercial enterprises that use such substances are kept up to date, and that, in order to enhance the receptiveness of the worker to a specific program: 1) where appropriate, the immediate community should also be informed through local health and other authorities of the hazard; and 2) the fundament*i o* --rarcous substances in the en vironment should be introduced in primary and secondary school curricula. The Decision to Inform Because the decision to inform those in affected workplaces of a chemical's hazard involves a commitment of substantial resources, the Committee considered it essential that a single national source, such as the Department of Health, Education, and Welfare, be charged with making that decision. The Committee noted that it should be, to the extent pos sible, a source that is credible to both management and labor--hence, the Committee said, one not involved in the regulatory process. It was also noted that the decision source should be close to the realities of the workplace, so that it could make an appropriate assessment of risk-- at least, the source should announce its decision in a form that could be translated to a specific occupational situation. Information Sources and Manner of Presentation Th*s Cormittee noted that workers are exposed to many kinds of information about the workplace from a number of different sources that are perceived by the worker as having various degrees of expertise and credibility, included in tnese information sources are "official" ones such a* OSHA, and "unofficial" ones such as, industrial hygienists, tamily physicians, shop stewards, management, local newspaper columnists, family, and fellow workers. The Committee stated that, notwithstanding the official sources, it may be that unofficial sources are more influential in actually modifying the worker's decision and behavior with respect to the workplace. The Committee said, however, that it could not identify any data with respect to the effectiveness or credibility of various information sources and that, therefore, multiple sources and institutions should be used to transmit messages to the worker. It was noted by the Committee that OSHA has responsibilities for the promulgation of standards concerning the appraisal of employees and that N10SH, in its Criteria Documents, must address this same area. However, the Committee emphasized that there appeared to be no mechanism at present by which the distribution of appropriate documents to all places of employment could be ensured. In this regard, it stated that management and labor both play a role in presenting information to the worker and to the relevant audiences. 78 21910084 BFG17099 Concerning the manner of presenting information to the worker, several recommendations were made by the Committee. To ensure effective communication with the worker, sources beyond those charged with statutory responsibility should be involved--consideration should be given to labor unions; extension services of land-grant colleges and other adult educarion services; state, county, and municipal health de partments; and community oriented public service health groups. It was emphasized that, to be effective, information provided by these groups must be essentially the same. And in this regard, the Committee recom mended that a central national source of such information be established, adding that the output of this source should be credible to all who use it as a common base. Although the Committee realized that programs will differ, it said that it was clear that: The information program should be initiated at the pre-employment interview and presented recurrently, regardless of the stability of the work force. s Presentation of the information should take into account the nature of the specific work force--its size, structure, degree of training, etc. It was reconunendea that the media u~ed tw carry ipecitic messages be tailored to the audience, and that a variety of media and presentation methods might be used. The Committee suggested tht OSHA devote some of its resources to the support of studies that would identify the best presentation techniques for selected types of workplaces. Implications and On-going Programs It should be recognized that successful education programs must utilize existing resources of health education and behavior modification including, for example, the American Cancer Society, the national and community health agencies, and university resources located in the com munity. In particular, the cancer prevention and control programs of the National Cancer Institute's comprehensive cancer centers should be looked to as sources of specialized knowledge in regional collaborative efforts. A variety of published iformation is available concerning benavioral and motivational factors as they relate to nealth education. Some selected publications are included in the References for this chapter. Unfortunately, there is, at present, a dearth of models that re late practical experiences with worker populations exposed to carcinogenic substances to the behavioral and motivational factors that influence these populations towards positive health behavior. Such information is just now being developed in a few programs such as the cancer prevention program at the University of Louisville for vinyl chloride workers. The components 79 BFG17100 21910085 of this program with regard to the medical aspects were reviewed earlier in this chapter; however, an educational component for the program is being developed, and the results of this endeavor will be useful to in dividuals concerned with cancer control for vinyl chloride workers (as well as for workers exposed to other carcinogenic substances). The approach to education developed by the Louisville center involves the following areas: General information for: - All employees - Employee's families - Former employees. Specific educational information for: - Families of deceased workers. - Individuals at high risk. - Employees who have been retired or transferred because of known occupationally-related disorders. - Employees with specific nonoccupationally-ieiated health problems. Educational programs on self-destructive life styles con cerning smoking and alcohol. Counseling and rehabilitative programs. Professional education programs for: - Private and community physicians - Industrial nurses and paramedical personnel - Health care personnel - Internal program personnel. Additional services: - Computer printouts of information on file for each employee, made available to the employee's physician. m 80 BFG17101 21910086 - Development of specialized training brochures for workers describing the medical surveillance program. - Implementation of specialized meetings for: General plant information. Employees at high risk who have been removed from the main plant and given other jobs. The families of workers. - Development of professional and community education programs for information exchange involving air pol lution boards, industrial medical personnel, the National Academy of Sciences, and the National Research Council. - Organization of a seminar workshop entitled, "Detection and Prevention of Industrial Chemical Carcinogenesis-- Vinyl Chloride Mode." - Fostering development of community educational programs to assist both business svi the general c.uununity U> understand the cancer control program's goals aud objectives. - Development of a joint program with the B. F. Goodrich Safety Division to motivate worker compliance with safety measures requiring the use of protective respirators. - Establishment of an advisory board composed of repre sentatives from the union, business, religious, legal, medical and scientific communities. The purpose of this board is to advise and evaluate the education of industry and the general public concerning environmental carcino genic hazards. Another major resource in the formulation and implementation of an educational program for the control of cancer caused by vinyl chloride exposure is tne Cancer Centers program of the National Cancer Institute (NCI). Under the terms of this program, the NCI funds centers of cancer research and development throughout the United States that meet certain criteria set forth by the agency. The NCI intends that these centers be geographically well distributed to maximize the benefits of their programs to the entire U.S. population. 81 BFG17102 21910087 The increasing interest of other federal agencies in the area of education is being manifested. In 1977, the National Institute for Occupational Safety and Health (N10SH) solicited proposals for a study to be entitled "Behavioral Procedures for Reducing Worker Exposure to Carcinogens." The stated purpose of the proposal was to develop and test an employee motivation program that would ensure healthful work practices which, in turn, could reduce exposure to carcinogenic agents. 82 BFG17103 Z191O083 Chapter VI A VINYL CHLORIDE CONTROL PROGRAM FOR A TOWN OF 25.000--A SCENARIO The setting is a vinyl chloride polymerization (PVC) plant located in a town of about 25,000 population. Although the plant was originally built in a very sparsely populated area at the edge of town, the town's growth has resulted in construction of homes near the plant fence line. Over the years, the plant had never been considered a community nui sance, only occasionally emitting visible smoke or vapor. At times, es pecially on hot, humid days, detectable though not particularly unpleasant odors were noted by drivers passing the plant. The plant uses large quantities of water from a moderate-size river that flows past the town and, during the first couple of decades of oper ation, plant effluents passed without treatment directly into the town's sewage tretment system (which, in turn, discharges effluents into the river). About ten years ago, the PVC plant constructed a small treatment facility, primarily to remove solids from the effluent prior to its release into the town's system. The community now acknowledges that the plant, during scvorsi deca-i?* of operation, nas released \?inyl chloride gas into che general environment in quantities not precisely known but believed to be significant. The community also acknowledges that the plant's management has recently acted to minimize this discharge, but there are some cynical citizens who feel that scant attention has been paid to this problem other than to avoid a loss of revenue by loss of a useful raw material. At the same time, however, the PVC plant has always been well-managed and, historically, has been considered by the community to be a good place to work. Accordingly, the labor turnover rate of about 10Z a year is somewhat less than average. The plant workforce has grown from the origi nal 75, of which between 50 and 60 are still employed, to a workforce of about 150. The workers are unionized, with relatively powerful leadership capable of effective negotiations with the management. The town boasts three hospitals and a modern public health clinic (all of which also serve the surrounding area). There is a local office of the American Cancer Society and the County Medical Society, the latter having appointed an Environmental Health Committee several years ago. The County Health Department, which receives little help from the chronically underbudgeted state health department, is a source of some pride to the community due to its recognized competence in most fields of publie health. There are a number of citizen's groups and social organizations, many quite active and some concerned with questions of environmental protection. 83 BFG17104 21910089 There is a small college (without a medical center). The media is repre sented by, in the town itself, a daily and a weekly newspaper, four radio stations, and a television station. The town and surrounding community are also served by metropolitan newspaper, radio, and TV. The text below outlines generally what was done by community organi zations to create a comprehensive vinyl chloride control program following the report in 1974 that forcefully linked vinyl chloride exposure with angiosarcoma of the liver. The County Medical Society The County Medical Society's Environmental Health Committee, recog nizing the need for close communication between groups that would be involved in vinyl chloride cancer control, took the initiative to form a special Vinyl Chloride Advisory Committee. The committee's members include: A health educator from the college. An industrial hygienist from the County Health Department. An oncologist from a leading hospital in the area. The PVC plant manager. r.epre*entatives of the union, the American Car"-.* iety (ACS), and the Kiwanis Club (one of several citizen's groups particularly concerned with environmental nealth). This advisory group meets monthly for discussion and to coordinate and assist activities, and has been quite effective in reducing dupli cation of effort and encouraging cooperation. (Such a committee might have been created by any organization--e.g., the plant itself, the health department, the local college, or the American Cancer Society chapter.) One of the Advisory Committee's first acts was to set in motion the development of a formalized education program directed to workers at the PVC plant (discussed subsequently under "Plant Management"-). Mean while, the Medical Society, after educating local physicians on the poten tial hazards of exposure to vinyl chloride, encouraged them to obtain occupational histories from their patients in order to identify those at greater-than-average health risk and to record any unusual clinical find ings. Also, they were encouraged to include in their diagnostic workups those tests most helpful in identifying vinyl chloride injury. m The Medical Society also took it upon itself to communicate with those scientific investigators who are on the forefront of diagnostic in vestigation into vinyl chloride injury and transmitted their findings to the community physician. In this activity, the Society drew upon the 84 21910090 BFG17105 resources of the Cancer Information Service (CIS), a service affiliated with the Comprehensive Cancer Centers recognized by the National Cancer Institute (see Figure 8) and with the .American Cancer Society. Working with the CIS by telephone, the Society has been receiving up-to-date information on research on the detection, treatment, and prevention of cancer and on the rehabilitation of afflicted patients. A listing of the CIS offices is given in Table 17. Another helpful resource to the Medical Society was the group at the University of Louisville ir Ken tucky that has established, with support from the NCI, an extensive medical surveillance and screening program for the workers at the B. F. Goodrich plant in Louisville. Other federal agencies concerned with cases of possible vinvlchloride-related disease--National Institute for Occupational Safety and Health (NIOSH), Food and Drug Administration (FDA), Occupational Safety and Health Administration (OSHA)--were referred to by the Medical Society. (See Appendix C for location of these aeencies.) Countv Health Department The County Health Department began to monitor ambient air levels of vinyl chloride in the community, with emphasis, of course, on monitor ing near the plant site. Eoth ambient air and stack emissions are Deing tested and recorded. Levels of vinyl chloride in the waste water efflu ents from the plant ait monitored systematically, as is the solid waste chat is deposited in community waste disposal areas. Working with infor mation ootained fom the district Environmental Protection Agency and Food and Drug Administration offices, the Health Department also monitors food and drinking water to help ensure chat regulations are being enforced. Coordinating with the other members of the Vinyl Chloride Advisory Committee, the Health Department issues news releases--carefullv pre pared so as not to cause undue alarm--to the locaL and regional media. The news releases are a major component of the program to convey informa tion about vinyl chloride to tne general puolic. The nealtn hazard repre sented by vinyl cnloride also has been included in tne health education program in tne schools. Also, the Health Department cooperates with the Medical Society in disseminating information to physicians in the community. The Department has also set up small but effective epidemiological studies utilizing its own records and reports from community physicians and hospitals. Finally, the Department's personnel have provided.assistance on medical surveillance activities and nelped the PVC plant management in estaolisning control programs to reduce exposure to workers and to reduce emissions to tne community. 35 BFG17106 21910091 M IN N E S O T A BFG17107 N F* CO H Oo CO N Table 17 NATIONAL CANCER INFORMATION SERVICE CALIFORNIA LAC-USC Cancer Center From Area Codes (213), (714) and (805): 1-800-252-9066 Rest of California: (213) 226-2374 COLORADO Colorado Regional Cancer Center 1-800-332-1850 CONNECTICUT Yale University Comprehensive Cancer Center 1-800-922-0824 DELAWARE Fox Chase Cancer Center 800-523-3586 DISTRICT OF COLUMBIA (Includes suburban Maryland and Northern Virginia) Cancer Communications for Metropolitan Washington (202) 232-2833 FLORIDA Comprehensive Cancer Center for the State of Florida Florida: 1-800-432-5953 Dade County: (305) 547-6920 ILLINOIS Illinois Cancer Council Illinois: 800-972-0586 Chicago: (312) 346-9813 MAINE Maine Cancer Information Center 1-800-225-7034 87 BFG17108 21910093 Table 17 (Continued) MARYLAND The Johns Hopkins Oncology Center 8CC-L54-14A4 MASSACHUSETTS Massachusetts Cancer Information Service 1-800-952-7420 MINNESOTA Minnesota Cancer Council 1-800-582-5262 MONTANA Montana Cancer Information Service 1-800-525-0231 NEW HAMPSHIRE i-800-225-7034 NEW JERSEY Fox Chase Cancer Center 800-523-3586 NEW MEXICO New Mexico Cancer Information Service 1-800-525-0231 NEW YORK Roswell Park Memorial Institute New York State: 1-800-462-7255 Erie County: (716) 845-4400 NEW YORK CITY Memorial Sloan-Kettering Cancer Center (212) 794-7982 NORTH CAROLINA Duke Comprehensive Cancer Center North Carolina: 800-672-0943 Durham County: (919) 286-2266 88 BFG17109 21910094 ( Table 17 (Concluded) PENNSYLVANIA Fox Chase Cancer Center 300-822-3963 TEXAS 11. 0. Anderson Hospital and Tumor Institute Texas: 1-800-392-2040 Houston: (713) 792-3245 WASHINGTON Fred Hutchinson Cancer Research Center Washington: 1-800-562-2575 Seattle Metro: (206) 284-7263 WISCONSIN Wisconsin Clinical Cancer Center University or Wisconsin 800-362-8038 WYOMING Wyoming Cancer Information Service 1-800-525-0231 Persons in states not listed can call the National Cancer Line: (800) 635-6694, Source: U.3. Department of Healtn, Education, and Welfare, Public Health Service, National Institutes of Health. N H* 89 (0 U1 BFG17U0 Plant Management First, plant management has recognized its responsibility to pro tect its employees and has developed controls that more than comply with Occupational Safety and Health Administration standards (i.e., vi nyl chloride levels inside the plant no greater than 1-ppm time-weighted average). This has entailed estabiis^irg environmental monitoring, desig nating regulated areas within th plant, and requiring strict standards of work practice. Also, plant management has effectively implemented emission controls to comply with EPA air emission regulations, and plant water effluents and solid wastes are monitored to ensure that only neg ligible quantities of vinyl chloride are released. Coincident with es tablishing production and emissio controls, the plant instituted educa tion and medical surveillance programs to help control the vinyl chloride health hazard. Educational Control With the advice and assistance of the Advisory Committee for Vinyl Chloride, plant management, in conjunction with the union, estab lished an education program to: Increase awareness of the hazards of working with vinyl chloride. Inform workers and their families on the nature oi controls used by the plant. ' # Motivate adherence to safety measures. Motivate participation in a medical surveillance program. Ihe target group for the educational program included not only the plant workers themselves, but also their families and retired workers and their families. (The plant was assisted by the Health Department in identifying and locating former employees for inclusion in the education and medical surveillance program.) The health educator on the Vinyl Chloride Advisory Committee was retained by the plant to coordinate, conduct, and evaluate the company's program. The educator's duties included enlisting the cooperation and assistance of the workers' union. The educational program includes information on the emotional aspects of exposure to a known chemical carcinogen, and it provides for personal counseling for both the workers and their families. Since many women in the community, especially wives of workers and women living near the plant, were concerned with reports that vinyl chloride has been ' linked with miscarriages and birth defects, the plant, in conjunction with the County Health Department and the Medical Sociey, took steps to 90 BFG17111 21910096 r inform the public about the (so far) tenuous nature of evidence for this hazard. In fact, the general educational program was extended to the public at large. For the general public, a telephone medical informa tion service was established by the advisory committee; this service in cluded tapes on the health effects and control of vinyl chloride, the PVC plant's program to control emissions and exposure to workers and to the community, and on cancer in general. For the continuing education of med ical and other health personnel in the community, tapes of a more technical nature were provided by the Medical Society. A recent progress review of the plant education program showed that a "critical-mass" point had been reached--!.e., current workers at the PVC plant, their families, former employees, and their families are knowledgeable about the vinyl chloride hazard, the nature of controls used at the plant, and the necessary safety measures to be continuously taken; also, all targeted persons were participating in the medical sur veillance program. Hence, it was possible to reduce the level of formal, direct, effort to the level necessary to convey occasional new items of information, sustain motivation toward safety measures and medical sur veillance, and to educate new workers. J.edical Surveillance Although a formalized plant medical program has been in exis tence at the PVC plant for a number of years, the findings on vinyl cnloride as a cause of angiosarcoma in tne liver prompted the establish ment of a more closely defined program of medical surveillance, including appropriate biochemical, radiographic, and functional diagnostic procedures. The medical surveillance program established by the plant man agement now conforms to the best state of the art currently available-a conformance which is complicated by the fact tnat the state of the art changes often and, with regard to the major bodily organ of concern, the liver, is in an early stage of development. Hence, the plant physician directing the program is in contact with the University of Louisville group that is actively involved in medical surveillance of vinyl chloride workers, as well as with other sources of information related to his medi cal surveillance function, such as the Medical Society, the state health department, the National Cancer Institute, NIOSH, and GSHA. An epidemiologic investigation undertaken at the plant has not, so far, shown any clearcut evidence of vinyl chloride-related in jury among the employees. The Plant Union The union leadership at the PVC plant played a major role in the entire picture of vinyl chloride control. Since it is to their unions 91 BFG17112 21910097 V " Aj* Vve*_ i Sa^ T . . APPENDICES 21910098 . : '*. . 3* v. . BFG17113 j H t,hat workers and their families often turn to for advice of many kinds, the plant's union leadership kept itself well informed on the vinyl chlo ride problem and was in constant contact with plant management, the plant physician, and with outside sources of information. It lent its strength to, and assisted in developing and implementing, the educational program for workers and their families. American Cancer Society The local American Cancer Society carried much of the educational burden in reaching the community in general. It also assisted in the pro gram for education of the PVC plant's workers and their families. The vinyl chloride problem was incorporated into an existing ACS program to approach the community regarding cancer prevention in general. 92 BFG17114 21910099 ( Appendix A VINYL CHLORIDE-RELATED COMPOUNDS The evidence that vinyl chloride is a carcinogen in man and animals raises tne question of the possible carcinogenicity of other related chemi cals in the industrial setting and general environment. The two tables that follow list chemicals that are structurally related to vinyl chloride. These chemicals met one of the following criteria: - Presence of vinyl chloride moiety. - Presence of a substituted vinyl group in which substitution is a potential leaving group approximately equivalent to chloride. - Structure may be a possible vinyl chloride metabolite. A-l BFG17115 21910100 CBDS CAS Number Number Chemical Name -- 75014 Vinyl chloride U.S. Production 1973 (grams) 2.43 x 1012 Structural Criteria! 2 -- 108054 Vinyl acetate C04580 127184 Tetrachloroethylene 6.82 x 1011 3.20 x 1011 1 1 C04546 79016 Trichloroethylene C50522 126998 2-Chlorobutadiene -- 75354 Vinylidene chloride C08264 79118 Chloroacetic acid C50135 107073 Chloroethanol -- -- Dichlorobutadiene 2.05 x 1011 1.8 x 1011 1974 (est) 7.7 x 1010 1974 (est) 2.21 x 1010 1972 ** ** 1 1 3 3 1 1 -- -- -- C50373 -- -- 926578 78886 96195 593602 107200 540590 1,3-Dichloro-2-butene 2,3-Dichloropropene 1,2,3-Trichloropropene Viny1 bromide Chloroacetaldehyde 1,2,-Dichloroethylene ** ** __ 5 __S 1 1 2 3 1 1 -- -- Vinyl iodide 2 -- 105384 Vinyl propionate 2 wFrom 1973 Synthetic Organic Chemicals (U.S. Trade Comm.). T NC z" ' Nci CH2 * CH-X where X is a potential leaving group approximately equiv alent to Cl. Possible vinyl chloride metabolite. **The chemical is listed in the 1973 Synthetic Organic Chemical**, but sep arate data are not given. This implies that annual production is greater. than 1000 pounds or $1000. ^Not in SOC--This implies that annual production is less than 1000 pounds or $1000. A-2 21910101 BFG17116 Appendix 5 ONE PVC PRODUCER'S APPROACH TO EVALUATION' AND CONTROL OF VINYL CHLORIDE EXPOSURE One of che U.S. producers of PVC, cne Eleanors Chemical Division or The Pantasote Company of New York, Inc., recently inaugurated an inno vative system for evaluating and controlling the exposure of workers to vinyl chloride. Description of the System The Pantasote system yields real-time information on exposure by obtaining data at intervals of several minutes for each workplace. A computer programming system prints a time-weighted average (T'.IA) for each work area sampled. The system obviates the requirement for daily sampling of individual workers, and it replaces the charcoal tube sampler with a more rapid and accurate evaluating system. This rapid, continuous survey and evaluation technique is coupled with alarms, care ful maintenance of equipment, and a stern policy of rule enforcement by the company's management. The actual sampling tine for each work area (or group of work areas; requires only 2 seconds. The frequency of sampling is a factor of tne numoer of stations and cne concentration of vinyl cnloride. stations snowing a sample value of more tnan 5 ppm are resampled to aeternine tne accuracy of cne sample. As stated aoove, the system princs out i-hour T.vAs tor eacr. area; but in addition, its memory carries ana princs out o-nour TAas for maintenance men or ocner individuals wno visic anv sampling area during cneir work. this program is deemed to meet che requirements of tne CSriA vinyl cnloride scandara at Gctooer 4, 1574, Section III (4) ..cnitcring: (4) Tne standard requires that cne individual employee exposure levels are to oe determined. This may be by personal or area monitoring, just so it is done with a 95^ confidence levs 1. rtiso in the Standard Section 1910.1C17(d)( 1; and (4): (a) (1)--A program of initial monitoring and measurement snail oe undertaken in eacn estaolisnment to determine if tr.ere is any employee exposed, in excess of che action level, witnout regard to the use of respirators. 3-1 BFG17U7 z0T0T6TZ (d) (4)--The method of monitoring and measurement shall have an accuracy (with a confidence level of 95 percent) of not less than plus or minus 50 percent from 0.25 through 0.5 ppm, tnrough 1.0 ppm, and plus or minus 25 percent over 1.0 ppm. (Methods meeting these accuracy require ments are availaole in the "NIOSH Manual of Analytical Methods.'1) Major Stages in Developing the System A comprenensive and thorough evaluation of vinyl chloride concentrations was undertaken in all areas of the plant where exposure was likely to occur. The evaluation extended over several months, and hundreds of samples were taken. The NIOSH method, using personal samplers with charcoal ad sorption of the vinyl chloride and subsequent analysis by gas chromatography, was used to determine personal exposure in the areas of potential exposure. Studies of air movement were made to determine the paths and velocities of contaminated air streams within the buildings. The early studies of vinyl chloride concentration, coupled with knowledge of air movement patterns, served to locate areas of nign exposure and units of equipment that needed maintenance. When indicated equipment repairs nad been made, the sampling program was repeated. Sampling and maintenance continued until exposure within the plant was controlled to a minimum. At this point, the excursions of high exposure found were attributed to human failure. After ".he proceeding evaluation and control procedure was completed, cne next stage of the company's program was to: establish pBi.aioi.cut sampling stations; develop a dystem of sampling and analysis to give real-time evaluations; ana attune the system to yield the 952 confidence level re quired to OJHA regulations. A portable gas chromatograph with flame ionization detector system was used to pinpoint leaks. It lacked the capability however, to measure or locate random excursions so as to facilitate the use of rapid corrective procedures. The need was indicated for a continuous rapid monitoring system that would pinpoint excursions in real time at any of the sampling locations. This would enable the evacuation of employees if necessary and allow for repairs to be undertaken. The Infrared Spectral Resolution gas phase spectrometer had the appro priate capabilities and the sensitivity to determine concentrations in low parts per billion in a metter of seconds. It could be programmed to provide: B-2 BFG17118 21910103 r Measurements virtually immune from interferences and thus accurate monitoring without either false low or high readings. Monitoring of excursions and 8-hour TWAs. Data for permanent hard-copy records in easy-to-read engineering units, maintaining a format of excursion levels and 8-hour TWAs. The instrument was supplemented with an appropriate system of data gathering and analysis including the reporting of operational information relating to plant concentration values, alarm annunciation, and employee exposure (TWA). The data acquisition system: Accepts data from the sensor measurements and converts them into concentration units. Determines if alarm levels are needed. a Interacts automatically with the system operator to alter the sampling sequence of measurements based on current concentration values so as to allow more measurement of areas and sample locations wnere high potential exposure hazards exist. Based on the particular situation and sampling algorithm, the system automatically tests (measures) adjacent sample locations in the vicinity of an excuts ion ana increase*, trie frequency oi sampling measurements for that pointAll alarm conditions are printed out. Checklist for Setting Up a Continuous Monitoring System Setting up a continuous monitoring system must be done systematicaly to quantify the environment of a plant. The following is a checklist for use in setting up such a system. Make a preliminary charcoal survey. Repair obvious leaks ascertained from the data obtained in preliminary survey and from use of the gas chromatograph flame ionization detector. Divide plant into study areas of approximately equal size, and monitor cycles of operation at each station; repeat each sampling cycle at 15-minute intervals as a minimum (maximum of 30-minute intervals). Statistically analyze results to determine areas for perma- * nent sampling stations. Provide a sample probe and a continuous sampling program that samples each probe for a predetermined length of time. B-3 BFG17119 21910104  Conduct a time-notion study to quantify probability of an employee with a specific job title being in a given area. ( a Sample an area for a period of 16 to 24 hours during normal operation. a Continue this preliminary analysis until the exposure con centration and patterns for the plant are clearly defined. To recap--obtain these three sets of data: concentration in an area as a function of time; probability of an excur sion in an area; probability of an employee with a given job title being in a given area. a Establish a correlation of monitor results and charcoal tube results by continuously sampling with charcoal tubes a num ber of individuals in areas being monitored. a Determine (after the equivalency of the two sampling methods is established) the amount of monitoring required to evaluate employees' exposure to within 25Z with a 95Z confidence level. a Determine, through sampling, the variation of vinyl chloride concentration with time; i.e., chances of negative, zero, and high concentration. a Determine through time studies the work path and practice for each operator or worker in the contaminated area; compute the actual-time wl.i.'iu--the area, using time study nd sample data to determine a TWA tor each employee for short periods, (15 minutes;, longer periods (1 iuu*-) and for an 8-hour work day. a Program the system so that it responds to the plant environ ment with variations in frequency of sampling--i.e., using its probabilistic intelligence, the system will hunt for excursions, thereby biasing areas of high chance of excur sion and minimizing the amount of time required to moni tor low-chance areas. a Set up the systems to print out reports of 15-minute TWAs at each sampling point and at a given time each day; or, for each 8 hours, to print out the average length or num ber of each excursion and TWA, for each station, and for specific individuals--i.e., maintenance or supervisory personnel that are in many work places in an 8-hour shift. a Program the system to a three-alarm level--a Blue alert when a concentration of 5 ppm is reached, a Yellow alert at a concentration of 25 ppm, and a Red alert at 1000 ppm, at which time the building is to be evacuated. B-4 BFG17120 21910105  Design che system for continuous monitoring without operator assistance and for programming of all items previously listed. Install analytical equipment that is fast, accurate, and specific. Design sample handling to be fast, self-cleaning, and contin uous. It is apparent that such a system--operating continuously in the po tential exposure area, determining concentrations and TWAs at 15-minute intervals, surveying areas of potential excursions at frequent intervals, and printing out data as previously described--will provide surveillance of real-time exposure in a vinyl chloride plant superior to that of the charcoal tube. B-5 BFG17121 21910106 17. Tabershaw IR, Gaffey WR: Mortality study of workers in the manufac ture of vinyl chloride and its polymers. JOM 16:509-518, 1974. 18. Anon: Epidemiological study of vinyl chloride workers--final report. Rockville, Md., Equitable Environmental Health, Inc., January 1978. 19. Monson RR, et al: Proportional mortality among vinyl chloride work ers. Lancet 2:397-398, 1974. 20. Falk H, et al: Mortality among vinyl chloride workers. Lancet ii: 784-785, 1974. 21. Nicholson WJ, et al: Mortality experience of a cohort of vinyl chloride-polyvinyl chloride workers. Ann NY Acad Sci 246:225-230, 1975. 22. Ott MG, et al: Vinyl chloride exposure in a controlled industrial environment: A long-term mortality experience in 594 employees. Arch Environ Hlth 30:333-339, 1975. 23. Holder b: Dow Chemical Co.: Testimony presented at Public Hearing on Proposed Standard for Occupational Exposure to Vinyl Chloride, U.S. Department of Labor, Washington, D.C., June 25, 1974. 24. Duck BW, et al: Mortality study of workers in a polyvinyl chloride production plant. Lancet ii:1197-1199, 1975. 25. Waxweiler RJ, et al: Neoplastic risk among workers exposed to vinyl chloride. Ann NY Acad Sci 271:40-48, 1976. 26. Manuelidis EE, Solitaire GB: Glioblastoma multiforme in pathology of tne nervous system. J. Minckleve (ed.), Vol. 2, McGraw-Hill, New York, 1971. 27. Pasternack BS: A proportional mortality study of workers exposed to vinyl chloride, 1947-74. [Firestone Tire & Rubber Company] Testi mony presented at Public Hearing on Proposed Standard for Occupational Exposure to Vinyl Chloride, U.S. Department of Labor, Washington, D.C., June 25, 1974. 28. Infante PF: Oncogenic and mutagenic risks in communities with poly vinyl chloride production facilities. Ann NY Acad Sci 271:49-57, 1976. CHAPTER V 1. The Industrial Environment: Its Evaluation and Control. U.S. Depar ment of Health, Education, and Welfare, National Institute for Occu pational Safety and Healtn. Washington, D.C., U.S. Govt Print Off, 1973. D-7 BFG Ylrt1 9TT0T6tZ s 63. Salvini MS; Binaschi S; and Riva M: Evaluation of the Psychophysiological Functions in Human Exposed to Trichloroethylene, British Journal of Industrial Medicine, 28, 293-295, 1971. 64. Sleight RB, Cook KG: Problems in Occupational Safety and Health, Center for Disease Control, U.S. DHEW (NIOSH), Cincinnati, 1974. 65. Special Report: Operator Training/OSHA's Hidden Failure, Modern Materials Handling Magazine, 45-60, October, 1975. 66. Wakefield J: Cancer and Public Education, London, Pitman Medical Publishing Company LTD., 1962. 67. Weaver NK: Measures for the Prevention of Occupational Cancer, Journal of Occupational Medicine, 18, 607-610, 1976. 68. Wynder EL, Mabuchi K: Etiological and Preventive Aspects of Human Cancer, Preventive Medicine 1, 300-334, 1972. 69. Young, MAC: Review of Research and Studies Related to Health Education Practice - What People Know, Believe and do about Health, Health Education Monograph, No. 23, 1967. D-12 BFG17135 21910120 HEALTH EFFECTS OF VINYL CHLORIDE Carlo I. Tosburro, 8.D. Dear Customer, Onlvarritr of leulitl Rurrltion Section, 51 Because of the condition of the Louisville, Kentucky original, this is the best copy that could be made. i nmtoopcnoH Vinyl Chloride-Associ. Vinyl chloride.(CH, olecule or nonoaef el basic u been eoe of the Boat : dusety for over e quii for both cheoical toxicit? end in snlaals. tepoi ence of thromboeytopi hematological dlaordei rela of the distal pbalangi scribed. Abnormalities in pulmonary functional capability and cardiac arrythnlas associated with Its use as an anasthetle have also been noted, the Most widelyknowndlserdera Include hepatic fibrosis, pellosls bepotls, bepatoaegsly, splenomegaly, portal hypertension, end hepatic angiosarcoma (1). There is at present some epidemiological and histo logical data that large clear cell carcinoma of the lung and neuro- falaatone of the brain ara also associated with exposure to vinyl chlo ride. Vlnvl Chloride-Associated Injury In Animals Many of those lesions hsva also basn dsscrlbsd snd shown to develop In ` animals exposed to vinyl chloride. In addition to the liver angiosar comas snd ths brain neuroblastomas, vinyl chlorlde-sxposed rata snd mice have shown Zymbal gland (sweat gland) carcinomas, nephroblastomas, subcutaneous angiomas, skin carcinomas, snd s variety of adenomas of die breast, pituitary glands, snd other assorted sarcomas of die ovary, pul monary, and uterus. A simple sunary of cancers by site la vinyl chloride workers in our cohort who had worked more than one year in shewn in Table 1. This research la supported by Contract No. R01-CK-S5212 from the Rational Cancer Institute, Cancer Control branch. Tei Reports on Btolony snd Htdlclne, Vo). 37. 1978 TZT0T6TZ BFGm36 Health Effects of Vinyl Cbluride/Tamburro 127 UPDATE OF NEK MEDICAL FINTIN'CS RELATED TO VliffL CHLORIDE A. Histological Sequences of Injury; The hepatic lesions in the humans and in animals related to prolonged exposure to vinyl chloride have been fairly well characterized. One of che earliest findings is "activation" or morphological changes in the sinusoidal lining cells without evidence of hepatocellular toxicity. These morphological changes in the sinusoidal lining cells are not usually associated with an inflammatory process or evidences of localised necrosis. The more advanced lesions are associated with an increase in subcapsular fibrosis with subcapsular bile duct proliferation, which causes the liver surface to appear "pitted" with small white scars when viewed at laparotomy or by peritoneoscopy. These lesions are associated with increased portal fibrosis of varying degree most often rounded in shape on the cut surface arid only rarely showing short stellate radia tion into the parenchyma. The lobular architecture, in general, is pre served, with the central vein areas being devoid of excessive collagen deposition, as Illustrated in Figure 1. The sinusoidal lining cells tend to be helmet shaped, have triangular nuclei and appear to be asso ciated with increased deposition of collagen in adjacent sinusoidal spaces. In addition, there is a focal sinusoidal dilatation within tlie lobular architecture often associated with bi-nuclear hepatocytes, sug gesting active regeneration of the hepatocytes. More recently. Dr. Bans Popper has described focal areas of hepacocyclc hyperplasia consisting of two or three cell chick plates, not associated with lobular fibrosis and regeneration as seen in alcoholic and viral injuries. With progres sive exposure to vinyl chloride, there appears to develop increasing atypla of the sinusoidal lining cells, progressive worsening of the focal sinusoidal dilatation (Figure 2), and ultimately, the malignant transformation of the sinusoidal lining cells (Figure 3). At present, it is not clear which of the sinusoidal lining cells (macrophage/Kupffer cell, flbroblast/Ito cell, or the sinusoidal endothelial lining cell) is the malignant stem cell which develops angiosarcoma. Most present data strongly suggests that it is che endothelial lining cell which ultlaiacely becomes malignant and forms che angiosarcoma. Further studies will be needed to verify this thesis. B. Biochemical Detection: Biochemical detection of these lesions has until recently, been mainly by traditional biochemical hepatocellular studies. These have included the alanine and aspartic aminotransferases (SGPT-SCOT), gamma glutamyl transpeptidase (GGTP), alkaline phosphatase, bilirubin (both direct and Indirect), and other enzymatic studies, such as sorbital dehydrogenase snd isocltric dehydrogenase. As illustrated in Figure A, our preliminary evaluation indicated that the ability of these traditional biochemical tests to predict the presence of underlying histological hepatocellular damage is at best 80-852 accurate -- the most effective of vhich is the alanine aminotransferase (SCPT). The gasma glutamyl transpeptidase is equally as effective but has a 6-82 false positivity; that is, abnor malities of the GGTP levels persist without histological or functional evidence of hepatocellular injury. Although elevations in alkaline phophatase most often reflected the more serious abnormality, in almost 21910122 Health Effects of Vinyl Chloride/Tamburro 128 one quarter of the Individuals, it was found to be normal In the presence of hepatocellular Injury. More recently, the Introduction of Indocyanine green (ICC), an anionic dye similar in Its physiological capabilities to Bromsulphalein (BSP), has increased our ability to identify mild and latent underlying chemical hepatocellular injury. Indocyanine green can be given in various dose levels for purposes of determining hepatic clearance. At the low dose, 0.5 ag/kg, its predictability is equal to that of the aminotransferases. By increasing the clearance dose to levels of 2.5 and/or 5.0 ag/kg, one can increase the ability to identify underlying hepatocellular injury to the 98-99Z range. A definitive biostatisdeal evaluation of both the specificity and sensitivity of indocyanine green, in comparison to Che traditional biochemical studies. Is now underway. Figure 5 illustrates the correlation found during preliminary studies between liver histology and dye clearance among vinyl chloride workers with Increasing degrees of total vinyl chloride exposure. This is further supported by the frequency of abnormal dye clearances at both the low 0.5 mg/kg and the high 5.0 mg/kg "clearance dose among vinyl chloride exposed workers (2). Although" these tests are very sensitive to identifying underlying disease, they have very poor specificity in identifying the causal agent and, because of this, are suited as screen ing tools rather than diagnostic ones. C. Various Tumor Types: Hepatic angiosarcoma, although appearing to be of a single cell origin, may be of multiple cell origins. Morphologically it occurs in a cellu lar, cavernous, and solid form. The cavernous and the solid tumor forms are most effectively detected by radioisotopic liver scans. In addition, diagnostic angiographic characteristics differentiate angiosarcoma from primary hepatocellular carcinomas, adenomas, cavernous hemangiomas, focal nodular hyperplasia, and macronodular regeneration of cirrhosis. Whelan et al.. have described the characteristic angiography and radio nuclide changes chat are characteristic of hepatic angiosarcoma (3). The tumors exhibit central hypovascularity with puddling and are surrounded by a peripheral stain which persists lace into the venous phase of the angiographic study. Radioisotopically this form of a tumor presents with a negative peripheral defect which, on occasion, may be missed on the anterior view of a scan but is seen on the lateral or posterior view. As demonstrated by Whelan al., healing hepatic in farcts secondary to wedged hepacic venography can create a false positive lesion on angiography similar to that seen in angiosarcomas. D. Non-Tumor Vascular Lesions: A second lesion often seen in the non-tuaorous portions of the liver is that of peliosis hepatis; it has been extensively described by Pliskin (A). These lesions tend to be numerous, involving the entire liver and have a diffuse stain throughout the nodules. The stain does persist into the late venous phase and may not be associated with any radioiso topic abnormalities of the liver scan. Whether these findings represent a pre-carcinogenic or pre-angiosarcoroatous lesion in vinyl chloride N H CD O K N QJ Health Effects of Vinyl Chloride/Tanburxo 129 workers Is still under study. E. Radioisotopic Detection: The ability of 99mTc sulfur colloid liver scan to detect anatooical lesions, based on the best siedlcal diagnosis, is supported by the find ings that, of the 19 cases with anatomical lesions, only three were radioisotopically reported as normal. In one of the throe reported normal cases, subsequent radioisotopic scans done three months later revealed the underlying abnormalities. What is equally important is that in the 957 "normal" individuals, the scan was reported as abnormal in only 32 cases. These data, therefore, illustrate an S4Z sensitivity (16/19) and a 972 specificity (925/976), with only a 32 false positive rate (32/957). This false positive race was markedly reduced in sub sequent years when repeated radioisotopic scans could be compared to initial baseline ones. It is our present opinion that the radioisotopic scan, either camera or rectolinear, represents the most effective means of identifying early anatomical lesions with the least degree of false positivity, thus preventing unnecessary diagnostic evaluation. The value and effectiveness of ultrasound versus the radiological isotopic scan as a screening procedure is under study. F. Associated Spleen Disorders: An enlargement of the spleen, as determined by radic(sotoplc scans (greater than 14 cm in longitudinal length) and verified by autopsy or laparotomy in 12 cases, has been seen in 602 of the Individuals with angiosarcoma and 402 of those individuals with the peliosls hepatis lesion. As illustrated in Figure 6 the correlation between spleen size and wedged hepatic vein pressure among vinyl chloride workers illustrated some disparities. At least 10-122 of those individuals with splenomegaly had no evidence of an elevated portal pressure as reflected by wedged hepatic vein pressure. In addition, angiographic studies demonstrated circular lesions in the spleen (lienal peliosls) which had persistent staining characteristics and were associated with a shortened celiec artery to portal vein circulation time and increased spleen scan size. The use of 99mTe sulfur colloid cleerance by both the liver and spleen gives further suggestive evidence that spleen macrophage cell activity might play a role in the splenomegaly and/or the vascular findings. In the individuals with lienal peliosls, there is a steep rise in the up take of 99mTc sulfur colloid by the spleen after initial recirculation. This may be due to either increased blood flow and/or increased total number of activated macrophaglc cells. Studies are now under way to further delineate these lesions. C. Lung Findings: The medical surveillance program has also illustrated the presence of an unusual lung finding among this cohort of vinyl chloride workers. The abnormality is characterized by a midzonal lateral pleural thickening, which, on histological examination, thus far has simply illustrated fat and fibrosis. The importance of this finding in approximately 42 of the work force may be non-occupational but regional, l.e., ocher environmental pollutants, infections, etc. These lesions do not appear to be BFG17139 N CD R Health Effects of Vinyl Chloridc/Taoburro 130 associated with any pulnonary functional disorders; and their signifi cance and relationship to sacking, tuberculosis, asbestosis, fungal in fection or possible geographic non-occupatlonal environmental pollutants are under study. There is, however, preliminary epidemiological and histological data that strongly suggests an increase in the frequency of lung cancer among vinyl chloride industrial workers. Falk and associates have been study ing Che incidence of large clear cell carcinoma occurring among vinyl chloride polymerization workers, which appears to be higher chan one would expect to find in Che general population matched for age, race, and sex. Preliminary studies using regional histologically matched lung cancer patients as controls indicate chat the occurrence of this partic ular cell type does not appear to be a geographic phenomena. Analysis is now underway to determine if there exists a correlation between this particular histological cell type and the work exposure history of this cohort population. The correlation, if any, between our pleural findings and this cellular type of lung cancer has yet to be determined. METABOLIC/PATHOGEMZSIS UPDATE ON VKfYl CHLORIDE Our present knowledge of the metabolism and pathogenic mechanism by which vinyl chloride Induces hepatic lesions may best be summarized byTablell. At concentrations of less than 50 ppm, vinyl chloride appears to be metabolized by the alcohol dehydrogenase system. At levels in the range of 200 ppm, oxidation appears to occur by the peroxidase - catalase system. Ulth higher levels, the mixed function oxidase system appears to be the major route of oxidation of vinyl chloride into its metabolic intermediates: chloroethylene oxide spontaneously rearranges to form chloroacetaldehyde, which is then further oxidized to monochloroacetic acid or converted to chloroethanol. Monochloroacetic acid is not seen in urine samples at low doses and may be only formed with higher ex posures of vinyl chloride. Chloroethanol and chloroacetaldehyde are most likely detoxified via the glutathione-cysteine conjugation system. This system, however, is saturable; and at higher levels, vinyl chloride Is excreted via the lungs unchanged (5). Elmore tt al., utilizing a modified Ames system and pure synthesized vinyl chloride intermediates, have shown that vinyl chloride, chloroethanol and chloroacetic acid are not mutagenic in their biological systems (6). This strongly supports the hypothesis that vinyl chloride monomer is neither hepatotoxic nor carcinogenic until it has been metabolized to its intermediate forms by the liver and/or other tissues. However, chloroacetaldehyde and chloro ethylene oxide were definitely found to be mutagenic, producing recom bination DNA defects in bacteria. These findings present difficulty in explaining why the hepatocyte, as the primary metabolic site for vinyl chloride, docs not undergo any significant evidence of hepatotoxicity nor malignant transformation. The adjacent sinusoidal lining cells oust either metabolize the vinyl chloride in a similar manner but have a less effective detoxification of the metabolite or receive from the hepatocyte the intermediate meta bolites, such as chloroethanol, which it may then convert to chloro acetaldehyde without being able to detoxify or further oxidize this mutagen. Although the hepatocyte is the primary site for vinyl chloride BFG17]40 K CD h* O K *\) Ln Health Effects of Vinyl Chloride/Tamburro 131 Mtabollsa, Its capacity to detoxify the vinyl chloride Intermediate metabolites may be the major reason It does not undergo malignant trans formation. Primary hepatocellular biochemical alterations observed during prolonged exposure to vinyl chloride In the rat may add further evidence to sup port this concept. Subeellular enzymes and metabolites were studied in animals exposed to 10-20,000 ppm of vinyl chloride ranging from 14-137 hours. Microsomal, mitochondrial, and cytosol enzymes. Including p450, NADPH cytochrome reductase and mixed function oxidase, were studied. Glutathione and glutathione reductase as oxidative and detoxification markers were also determined, in addition to the conventional clinical biochemical studies, which Included aspartate (SCOT) and alanine (SCPT) aminotransferase, alkaline phosphatase, bilirubin, lactic add dehydro genase, total protein, albumin, cholesterol and triglycerides. After 137 hours of exposure, no significant changes occurred in the mitochon drial or the microsomal enzymes nor In the glutathione content. There was an increase in the glutathione reductase at 30 hours and a signifi cant decrease In glucose-6-phosphatase (C-6-P) after 71 hours of exposure, followed with an Increase In glucose-6-phesphate dehydrogenase (G-6-PD). These biochemical findings occurred without evidence of histologically discernible changes in the conventional biochemical studies. This decrease in G-6-P and Increase In G-6-PD after "simulated" chronic exposure are very similar changes to those found by Ueber and Lee (7) In rapidly developing primary hepatocellular tumors. Their studies demonstrated a decrease in gluconeogenesis with a reduction in G-6-P and an Increase in G-6-PD and transaldolase. These biochemical changes were followed by an Increase In purine biosynthesis (Increased phosphorlbosylpyrophosphate aminotransferase - PRPP) and eventually an Increase In the production of ATP and CTP, leading to Increased nucleic acid synthesis. At the termination of our experiment (at 37 hours), there were no signif icant changes In PRPP; but studies are now underway exposing animals to up to 230 hours to determine if the hepatic enzyme biochemistry In vinyl chloride exposure is similar to chat seen in rapidly dividing primary hepatocellular tumors. It may well be chat these findings may represent an adaptation of the hepatocyte, with Increasing nucleic acid synthesis for purposes of repair, and may make these cells more susceptible to malignant transformation if the carcinogenic agent is unable to be re moved or detoxified with sufficient efficiency. In contrast, the sinu soidal lining cells may well be able to oxidize these metabolites but unable to detoxify them effectively and therefore be more susceptible to developing DNA injury. Studies have begun in our laboratory to isolate hepatocytea and the various sinusoidal lining cells and determine the individual cell types' ability to both oxidize vinyl chloride, as well as detoxify its Inter mediate metabolites. These studies, only recently begun, have already demonstrated unusual differences between the enzyme activity of hepatocytes versus mesenchymal cells. Our preliminary studies, which require further verification, failed to demonstrate mixed function oxidase activity (based on micromoles per minute per million cells) in contrast to the hepatocytes. Further purification of the mesenchymal cells and 21910125 BFG17141 Health Effects of Vinyl Chlorlde/Tamburro 132 verification of their cellular type must be done before sny definitive conclusions can be drawn from these preliminary observations. They do, however, suggest chat metabolic differences of the various cell types may play an important role in the ability of cells to oxidize and/or detoxify potential carcinogens. Pathogenesis via Human Case Studies; The co-factor role of such agents as alcohol in the pathogenesis of vinyl chloride carcinogenesis may be suggested by a naturally paired two-case study. Case A - Employee began to work in vinyl chloride polymerization plant in 1947 as a chemical operator. He worked in the polymerization process for 18 years, and estimated exposure during this time ranges from 50-10,000 ppm of vinyl chloride. He had a history of extensive alcohol consumption and was discharged from employment because of this in 1968. In 1962 he had the first clinical abnormalities related to liver injury, and these were identified histologically as being alcohol induced in 1964. Bis alcohol consumption was greater than 512 ec per day. Case B - This Individual was also employed in thg. same polymerization plant and began working at the same time and at the same Jobs and from 1947 until Case A was discharged 18 years later. Case B continued to work in poly merization plant process for an additional ten years at exposure ranges of 50-10,000 ppm. In 1974 during the medical surveillance program's initial phase, Case B was identified as having persistent biochemical abnormalities which were clinically and histologically shown to be due to vinyl chloride Injury and a developing cellular type of angiosarcoma. His alcohol consumption had been less than 50 cc per day. He did, however, have a history of malaria during his military service prior to vinyl chloride exposure and was transiently HB^Ag positive in 1974. Histologically, Case B was verified as having angiosarcoma. During the same year. Case A was shown to have evidences of both alcoholic injury with cirrhosis and the characteristic lesions of vinyl chloride injury, including subcapsular fibrosis with bile duct proliferation, peliosls hepatis, sinusoidal cell activation, focal sinusoidal dilatation and areas of rounded portal fibrosis. Histologically, the hepatocytes showed atypical change consistent with hepatocellular carcinoma and the sinu soidal lining cell changes characteristic of angiosarcomatous tissue. In these two case studies, in which the duration and degree of exposure was as identical as one could expect in human biological system, we have individuals developing tumors of two different cell types. It is sug gested from these findings ehat alcohol played a significant role in the hcpatocyte's inability to detoxify the vinyl chloride metabolites, there by causing DNA Injury and ultimately leading to the development of primary hepatocellular carcinoma. Some recent animal studies by Dr. Martha Radike and her group (8) in' Cincinnati have shown a four-fold Increase in hepatic tumors among alcohol-fed rats exposed to vinyl chloride In contrast to those exposed to vinyl chloride alone. The role of secondary or co-factors in the development of chemical carcinogenesis needs much further study, both in 21910127 BFG17142 Health Effects of Vinyl Chlorlde/Taaburro 133 animals and In human observations. The Importance of the hcpatocyte's ability to adequately metabolize vinyl chloride Is further illustrated by the preliminary reports of Dr. Hnltoni et j1.. (9), indicating that newborn rats exposed to vinyl chloride develop a four-fold Increase in primary hepatocellular cancer. In con trast, the adult rat of the same species develops angiosarcomas. Review of Prospective Medical Surveillance Svscem: It is highly unlikely that any singular approach to the understanding of the cheaiical carcinogenesis (l.e., chemical structure studies, animal experiments or human epidemiological studies) will completely succeed in characterizing the pathogenic sequence. Structural studies of chemicals can help direct attention to those agents which say be more carcinogenic. However, metabolic activation of chemicals also needs to be done and further studied in Ames-type bacterial systems to determine whether the metabolites arc the potential mutagen/carcinogens. Even with this in formation, the methods by which these agents produce cancer must be Illustrated in animals so that we may devjelop earlier and more effective means of prevention and screening of our industrial workers. Although vinyl chloride has demonstrated both in animals and humans almost identical histological and morphological changes, this illustra tion of animal model extrapolation to humans is by far the exception rather than the rule. It is, therefore, equally Important that one con tinue to gather accurate epidemiological data In a prospective fsshion, to determine the human variation from animal studies as well as to docu ment the effectiveness of our prevention methods and surveillance pro grams, which are often instituted on the basis of limited knowledge and in time of crisis. To this point, a prospective medical surveillance system hss been designed end initiated by the University of Louisville in collaboration with the B. F. Goodrich Company and its unions (Distil lery Workers Union, International Brotherhood of Electrical Workers, International Association of Machinist Workers, and Pipefitters Union). This prospective prototype system is based on the classification of in dustrial environments into three categories (10). Type A or possible carcinogenic: This would include those industries utilizing materials not yet studied for their carcinogenic potential. Type B or probably carcinogenic: This would include those industries utilizing a material or materials suspected to be potentially carcinogenic, type C or actual ly carcinogenic: This would include all industries utilizing a material known to be cancer-producing either in animals or man. The basic epidemiological data required from the various industrial categories is based upon the possible, probable or actual presence of a carcinogen. Those type A industrial environments would need to collect or record minimal epidemiological data, Almost 90S of which la already being recorded or collected by most industries for other socio-economic reasons and would require only minimum outlay of coat and personnel time. This basic data would include an employee work history, a job exposure history, and a medical illness history composed of three parts. First, a record of previous medical illnesses based on pre-employment history BFG17143 R CD R O R fN) 00 Health Effect* of Vinyl Chloride/Tamburro 134 and examination. Second, a record of all medical Illnesses and hospi talization during employment. In most cases, with certain modifications, this can be obtained by way of third party Insurance payments. Third, a company/plant-based mortality record based on Che diagnosis at time of death for each worker. Almost all of this information Is presently recorded and kept In various forms by chemical Industries (for business purposes), the medical care systems or as part of vital statistics. At the second level, Typ* a periodic medical hlacory and physical examination should be required; and, in addition, rank order monitoring should be performed for each job occupation where Individual chemical monitoring Is available. Where possible, area monitoring data should be utilized for these rank orderings, and preferably, when scientifically available. Individual monitoring would be substituted for the rank order system. Updating of Job classifications and job exposure Indices based on rank order determinations has already been done In actual Industrial environ ments at a cost of approximately SlO/person for the initial updating. The cost of maintenance of such records Is* estimated to be less than S3/ person/year employed. In Type C industries, those environments actually using carcinogens, regular history and physical examination will be required and performed with Increasing frequency as the duration of employment increases. In dividual monitoring should be used to determine the actual exposure. Where this Is not yet scientifically developed, efforts should be made to design usable monitors for this purpose. In Type C Industrial en vironments, collaborative and cooperative efforts among the industrial community, the labor force, and the scientific community are essential in order to allow an accurate, ongoing systematic collection and analysis of the epidemiological information. These data will help resolve the problems of safe exposure levels, frequency of screening needed, effec tiveness of screening, and the Identification and effect of co-factors upon individuals exposed to actual carcinogens. INDUSTRIAL HEALTH EDUCATION In order to accomplish this, expansion of educational programs vithin these industries is needed and must be continually improved and updated. Any industry working with possible carcinogens should have educational programs directed not only at their employees, but also their families, the managerial personnel, and union representatives. In those environ ments where probably carcinogens are involved, educational programs are needed for industrial medical personnel and para-medical personnel. This is especially important in those industries where Federal occupa tional laws require or an industry desires to institute a surveillance program. Finally, in those industrial environments where an actual carcinogen is In use, educational endeavors must be expanded beyond the industrial environment. These should include the local medical com munity (in order to help them better understand the medical surveillance service being rendered in relationship to the private physician's role in the care of the employees), the local community (relative to its potential danger), the business community, and the industrial community 21910129 BFG17144 Health Effects of Vinyl Chloridc/Tomburro 135 not involved in sinilnr use of carcinogens, so that they may better understand the health and safety of these enployees. The lack of under standing on the part of the non-involved business and industrial com munities can lead to unnecessary socio-economic stigmatisation or eco nomic difficulties. As evidence of the potential effectiveness of such medical surveillance systems in an actual carcinogenic environment. Table III illustrates the compliance rates for medical screening over the past three years. This high voluntary compliance on the part of the employees illustrates Che concern of the employees and the cooperative effectlveness of management and labor in identifying and correcting industrial problems. It has become clear in our past four years, that industry's need for scientific expertise and assistance must be coupled with the medical and scientific coBDunitles' better understanding of the work environment and its socio economic relationship. The conducting of medical surveillance programs on an ongoing, long-term basis requires adaptation of our present methods of medical screening so as not to cause unnecessary and excessive inter ference with the industrial function and at the same time deliver the best screening surveillance system ac the .lowest coat. Much more work is needed in adapting such syscems and demonstrating their implementability and their cost effectiveness. This is not a short-term endeavor and will require well thought out planning and a marked increase in the collaborative effort among Industry, the labor force, che local communi ty, and the scientific communities (local or regional ones). Regional and geographic cancer centers can play a major role in assisting and supporting, with scientific expertise, their local industries in en deavoring to better identify potential carcinogens and develop che most effective means of preventing both acute toxicity and long-cerm carcino genicity. SUMMARY Vinyl chloride is a basic chemical for plastics manufacturing and has been used as an anesthetic agent. Vinyl chloride's previously unknown carcinogenic capability appears to be related to the body's ability to convert it from a non-toxic or minimally toxic chemical to s toxic and, with prolonged exposure, cancer-forming agent. Early exposure in animals causes body cells to make adaptive changes which may prepare them for malignant transformation and appear to precede evidence of morphological injury. These findings appear to occur before a low-grade chemical in jury occurs. Vinyl chloride chemical Injury in man appears to follow the same pattern. Present clinical data in humans now demonstrate evi- dence of pre-cancer injury and cancer transformation of various types of .cells_J.n_different organs of the body.. .Manifestations of pre-cancerous injury to organs other chan the liver (such as the lung, heart, spleen, brain and*~lvmphatlc system) may also be occurring and require further ^gvgiiMJtioti. - Early detection of these pre-cancerous chemical injuries requires a prospective ongoing system of surveillance and che development of diag nostic methods which can identify specific causal agents in the presence of non-specific injury. Such a systematic approach has been developed and is now in operation. Its initial achievements appear to be the Z1910130 BFG17145 Health Effects of Vinyl Chloride/Tamburro 136 foundation for future success In controlling the health effects of in dustrial chemicals. REFERENCES 1. Sellkoff, I.J., Hammond, E.C., Eds: Toxicity of vinyl chloride polyvinyl chloride. Ann. NT Acad. Scl. 246:1-337. 1975. 2. Tamburro, C.H.: The hepatic role in carcinogenesis and Its early detection -- the vinyl chloride model. Tale Journal of Medicine and Biology (In press). 3. Whelan, J.C., Creech, J.L., Tamburro, C.H.: Angiographic and radio nuclide characteristics of hepatic angiosarcoma found In vinyl chloride workers. Radiology 118:549-577. 1976. 4. Pliskin, M.: Feliosis hepatis. Radiology 114:29-30, 1975. 5. Hefner, R.E., Jr., Wacanabe, P.C. Chring, P.J.: Preliminary studies of the fate of Inhaled vinyl chloride monomer in rats. Ann. NY Acad. Sci. 246:135-148. 1975. 6. Elmore, J.D., Wong, J.L., Laumbach, A.D., at al: Vinyl chloride mutagenicity via the metabolites chlorooxlrane and chloracetaldehyde monomer hydrate. Blochem. Biophys. Acta 442:405-419. 1976. 7. Weber, C., Lea, M.A.: The molecular correlation concept. In Methods In Cancer Research. Edited by N. H. Busch. NY, Academic Press Inc, j2:523-578, 1967. 8. Radike, M.: Personal communication. 9. Haltool, C.: Recent findings on the carcinogenicity of chlorinated olefins. Conference on Comparative Metabolism and Toxicity of Vinyl Chloride-related Compounds. National Institute of Environmental Health Sciences, NIH, May 2-4, 1977. 10. Greenberg, R. A., Tamburro, C.H., and Kupchella, C.E.: A prospec tive medical surveillance program for the detection and prevention of industrially related cancer. Prevention and Detection of Cancer, Vol. II., Ed: H.E. Nieburgs, Marcel Dekker, Inc., New York (In press, February, 1978). 21910131 BFG17146 Health Effect* of Vinyl Chlorlda/Tanburro 137 TABLE I CANCERS BY SITE IN POLYVINYL CHLORIDE PRODUCTION PLANT COHORT WORKING MORE THAN 1 YEAR WHO DIED DURING THEIR WORK PERIOD OR AFTER RETIREMENT. SITE LUN6 LIVER BRAIN COLON PANCREAS THYROID PROSTATE EYE UNKNOWN NUMBER 28 10 5 4 2 1 1 1 1 21910132 BFG17147 Health Effect* of Vinyl Chlorid/Ta*burro 138 PROPOSED VINYL CHLORIDE METABOLISM PATHWAY IN THE RAT 21910133 BFG17148 J / Health Effects of Vinyl Chloride/Taburro t** rcrs>. K> >- IL C/> Uzi U>I H K MCNi zm thns. cn *- o K% H CO 04 M pH CO tcon u ---- OUJ-- C<CQ c to o o 3Q. CD c_ o oenn u_ O Ui_>J <L>aU-: COzN 111 Is} oCoD LO4AO _ 4 co"o> m*4 Ci*n4O CO -<I o co K <o CO > M CO z >- zo x< g < CCOL - I Hoe soe o .3 UJ X COOf UI X oe o * oz >- o z < o O O 0 o oe UJ x 1 a<. h CO oa u>j><xxUJ o z u. 20 o > uj Z UJ < > oJZo a.-- xx ui o o LL O CO H UJ Z O UJ <z HO z a. uj OO Xo UJ Q. O z CO -- CO UJ zu<r H 0 o z< CO CQ OUJ O-5 X X UJ o> o-- OH o< K XH CO UJ -- >z mm OZ XO m< ui z X-- H UJ Z CO --o z UJ H CO <> UJ .J Xu -<J UJ -- oo UJ UJ a. zco 139 BFG17149 N H U> oH s "N \ MO Figure 1. Typical portal area showing increased portal fibrosis with mild bile duct proliferation, wich few inflacsnatorv cells mainly mono nuclear cell. (Low power x 100) BFO'1150 N ( hk O 03 or 141 Figure 2. Focal sinusoidal dilatation is seen with activated sinusoidal cells (arrows). Lobular architecture otherwise well preserved with normal appearing hepatocyte with some increased number of bi-nuclear hepatocytes. (Low power x 100) BFG17151 21910136 M2 Figure 3. Markedly atypical sinusoidal cell change with malignant transformation (arrows) and piling up of sinusoidal cells into sinu soidal spaces. (High power x 400) BFG17152 21910137 143 ICQ Figure 4. Frequency of biochemical abnormalities being present and correctly indicating the presence of significant histological abnor malities (SGPT " alanine aminotransferase; GCT " gamma glutamyl trsnspeptidase; ALK FHOS * Alkaline Phosphatase; SCOT aspartic aminotransferase; 1CD lsocltrlc dehydrogenase and ICG " indocyanine green clearance). CANCER >X>2 FAT PORTAL FIBROSIS <tO% RAT MMMAL FBROSIS MINOR CHANGES NORMAL LIVER 22*/.* '/. AS*/.* A3 */. 71% 7, WffM A AA AONOftMAL ICO A A AA A AA A*A * AAA AA A AAA A V *** A AA A AA A AA A A O-OJ LO-LS &0-U <LO*SJD AVERAGE VC EXPOSURE MDEX Figure S. Correlation between liver histology and Indocyanine dye clearance (0.5 mg and 5.0 mg dose) abnormalities in vinyl chloride workers with increasing vinyl chloride exposure as determined by average exposure index " 5n. E. where: Jn< " number of months at exposure 11 level E; Sni Ej; exposure rated on a rank order scale from 1 to 6 (1-lowest; 6hlghest) inA " total months services at VC plant 21910138 BFG17153 144 PERCENT OF PATIENTS 50 r 40 do 20 10 - I WHVP | 1 elevated I NORMAL enlarged! normal SPLEEN SIZE Figure The correlation between spleen sire end wedged hepatic vein pressurfjin vinyl|chloride workers. VV>? / 6GT0TGTZ BFG17154