Document 2qv4b3J5KdZB5oexeGJ37jeNN

October 1974 ON THE HORNS OF THE VINYL CHLORIDE DILEMMA by Paul H. Weaver Reprinted solely for the information of The B.F. Goodrich Company 1974 Time Inc. BFG65886 If government allows workers to be exposed to the gas, some of them may die. If it eliminates all exposure, a valuable industry may disappear. 1 ON THE HORNS OF THE VINYL CHLORIDE DILEMMA by Paul H. Weaver Not long ago, cancer and plastic were associated with each other only in the writings of Norman Mailer, where they serve as symbols of decadence and self-destructive ness in the high-technology society. Since January of this year a series of medical reports has shown this associa tion to be a real scientific fact as well. It is now clear that vinyl chloride, a gas from which the second most widely used U.S. plastic is made, causes a fatal cancer of blood vessel cells in the liver; the gas is also implicated in a host of additional diseases, ranging from gastrointestinal bleeding to chromosome damage. These discoveries have touched off a flurry of regula tory activity. The Food and Drug Administration, the En vironmental Protection Agency, and the Consumer Prod uct Safety Commission have all banned aerosol sprays using vinyl chloride as a propellant. But the measure that cuts deepest was taken by the Occupational Safety and Health Administration. OSHA has moved to reduce the permissible level of worker exposure to vinyl chloride in the plants where it is made or converted into plastic. Preparing for the iceberg In the course of these developments, it has become clear (hat our regulators have a hard time thinking sensibly about problems like vinyl chloride. The businessmen be ing regulated and the workers affected seem to find it no easier. The fact is that our society seems to have no agreed-upon standards for dealing w'ith situations in which medical and economic considerations collide headon. Since collisions of this sort will plainly be numerous in the years ahead--the vinyl chloride case is widely iden tified as the tip of an enormous regulatory iceberg--it seems useful to get clear on the issues involved. If vinyl chloride were an unimportant substance, or if it were known to be dangerous only in very high concen- Research associate: Sydney Ladensohn Stern trations, or if it were easy to keep human beings out of contact with it, there would be no particular problem. In that case the health danger could be completely elimi nated at little or no cost, and the question of what to do would answer itself. Unfortunately, the vinyl chloride issue isn't so simple. It seems to be very difficult and costly--and it may be im possible--to guarantee that no vinyl chloride worker will be exposed to the gas. Though no one knows for sure, it is possible that even very small exposures may cause sick ness or death. Yet it is also true that the plastics made from vinyl chloride are extremely important to the Amer ican economy. The market value of the gas being pro duced this year, and of the resin made from it, is perhaps $1.5 billion: the gas and resin industries together employ about 6,000 workers. But what most people think of as the "plastics industry"--the transformation of resins in to products--is a far larger operation. The total number of jobs involved in polyvinyl chloride (PVC) alone is about 320,000; the sales volume runs to many billions. And there are no entirely satisfactory substitutes for PVC at hand. Banning it would be certain to cause grave economic dislocations. Thus the regulators at OSHA are caught between the proverbial rock and a hard place. It is clear that their task should be to find the right "trade-offs"--to devise regulations in which the benefit of increased health for Th most hazardous job in polyvinyl chloride planti . : to be the cleaning of the vats in which vinyl chloride polyme- - PVC--that whitish resin at the worker's feet. Of the sixteen r cases of vmyl-chloride-related liver cancer, fourteen occurred - . i-ers. The job is presumably a lot less hazardous since the . -n of the respirators, protective clothing, and air evacuation <c- .:*. . the dan gling hose) that are shown here. The stainless-steel-' -own is in B.F. Goodrich s Pedricktown. New Jersey, plant, oer- c - -cst mod em in the U.S. The vat is entered and cleaned rta- . t once a month. Until recently vats in most older plants we--' t once or twice a day. ? ..KWBWy"1 1 BFG65887 "fy Groskinsky The View from NIOSH: Make It Safe On January 22, 1974, Dr. Maurice Johnson, environmental health direc tor for B. F. Goodrich, called on Marcus Key, director of the National Institute of Occupational Safety and Health. Johnson had a discovery to report. Three workers in Goodrich's Louisville polyvin3'l chloride plant had died from angiosarcoma of the liver since 1971. Key summoned his top aides, who agreed that they had an emergency on their hands. Two days later a small army led by NIOSH Standards Development chief Vernon Rose, invaded the Louisville plant to conduct the first of many "walk through" inspections. Within a week, Rose's task force had a list of recommendations for re ducing worker exposure to vinyl chloride: --protective coveralls, shoes, and gloves for workers exposed to PVC. --airtight suits and respirators for reactor cleaners. --daily showers for exposed workers. --a 50 parts per million suggested ceiling on vinyl chloride monomer exposure. Normally, writing a criteria doc ument--NIOSHese for a recommend ed standard--is an eighteen-month process involving exhaustive study. In this instance, however. Rose relied on guesswork and precedent. Assum ing that vinyl chloride causes cancer through inhalation and skin contact, he modeled his standards on those used earlier by NIOSH for industrial carcinogens. Aiming for a mid-March deadline, NIOSH organized a hectic series of meetings and studies. By the end of February, its toxicology group had been unable to determine the carcino genicity of VCM below 50 ppm. The medical group had suggested a bat tery of liver tests for PVC workers, but industry and labor had split over the exposure ceiling. Industry urged 50 ppm, which it knew it could achieve; labor advocated "no detect able level," refusing to treat workers as guinea pigs. In this situation. Rose simply toughened and expanded on his ear lier recommendations. Most impor tant, he decided that the ceiling for vinyl chloride be set at "no detectable level"--the only exposure he knew to be safe. "It is doubtful," he conceded in a memo to Key, "that any plant can show workroom levels of nondetected." To meet it, respirators would have to be worn at all times. He wasn't sure this was practical, but he was certain it was safe. On March 11, Dr. Key submitted NIOSH's recommendation to Assist ant Labor Secretary John Stender. When OSHA proposed its permanent standard two months later, it incor porated most of the NIOSH text ver batim, including the "no detectable level" provision. The View from Firestone: Make It Practical To Todd C. Walker, the towering, outspoken president of Firestone Plastics, OSHA's proposed standard was as much a crisis as the Goodrich bombshell had been to NIOSH. He was determined to resist the stand ard with "the maximum information" at the OSHA hearings in Washington, D.C., this summer. Walker assembled four task forces --legal, engineering, financial, and medical--to develop a Firestone-rec ommended standard on a crash basis. Four alternatives were to be studied: the interim 50-ppm standard, "nondetectable," and two intermediate levels chosen arbitrarily--40 ppm maximum with a time-weighted aver age ( TWA) of 25 ppm, and a 15-ppm ceiling with a TWA of 10 ppm. For each level the questions were: is it safe and is it feasible? Weeks later, the medical gro|up was unable to say positively that !any of the levels was unsafe. An epidemio logical study of Firestone's rubber and PVC workers showed no signifi cant differences, suggesting that 50 ppm was not relatively unsafe. The engineering group reported that the nondetectable level was un attainable. It also forwarded a cri tique of OSHA's proposed work prac tices. Protective clothing for all workers was unnecessary, it said, be cause PVC dust is not a carcinogen. VCM gas, which is, could be kept away from the skin only by air-tight suits, which would be "hot, cum bersome, expensive, and dangerous." OSHA's provision for air-supplied respirators for all exposed workers was also ill advised. These would be uncomfortable ("an instrument of torture"), fatiguing, probably haz ardous, and would interfere with work. One portable type weighs twenty-eight pounds and would have to be changed three times ari hour. Nonportable respirators could be used, but workers would be attached to air hoses (themselves a workplace hazard) and confined to a radius of less than fifty feet. The financial group reported that capital investment would have to double to attempt reaching a nonde tectable level. The legal staff conclud ed that OSHA's proposed standard was unfeasible and therefore illegal. When it came to deciding what level he would recommend. Walker had a problem. His medical evidence showed the three levels above non detectable to be equally safe. His en gineers said that the feasibility of the lowest of these (15-ppm ceiling with a 10-ppm TWA) was uncertain, and Walker ruled it out. Left with a choice between the two higher levels, he opted for the 40-ppm ceiling with a 25-ppm TWA to show that Firestone was willing to do more than the mini mum. Thus, with a practicality rem iniscent of NIOSH's decision to rec ommend a level it knew was safe, Firestone ended up recommending a level it knew it could achieve. BFG65889 4 workers is balanced against the increased cost to the plas tics industry and society as a whole. Unfortunately, this task has remained largely unacknowledged. OSHA probably will end up compromising on the de gree of exposure to the gas it will allow: its decision is apt to be announced this month. But the agency has been under terrific pressure to view the issue before it in ab solutist terms, as if its only legitimate concern were the preservation of absolute security for the vinyl plastics industry, or the achievement of perfect safety for vinyl chloride workers. For a while, it seemed a foregone conclusion that OSHA itself would opt for perfect safety. On May 10, it formally proposed that the new standard for vinyl chlor ide be set at "no detectable level," i.e., that no plant would be allowed to operate so long as any of the gas could be found in the air or in contact with workers. The industry replied, in effect, that any such standard would be techni cally impossible and economically disastrous, and that if OSHA went through with it, the polyvinyl chloride in dustry would be put out of business. OSHA's final decision will affect more than this single industry and its customers. The vinyl chloride issue may be viewed as the first major test case for a new movement in government regulation. The leaders of the movement are three of the newest federal regulatory agencies, all created since 1970: EPA, CPSC, and OSHA. One general idea behind all of these agencies is that business can no longer promiscuously pass on to society all the indirect costs of running a modern economy. As Sheldon VV. Sam uels, health director of the Industrial Union Department of the A.F.L.-C.I.O., put it, "The free ride on social costs is at an end. In the plastics industry you're seeing a manifestation of social costs." With jurisdiction over virtually every product and sub stance, these agencies, together with the FDA, are be ginning to use their sweeping powers to reduce the pub lic's risk of chronic disease, especially from industrial products. Some of the agencies are subjecting new sub stances to rigorous pretesting before they are allowed on to the market. And with the vinyl chloride case, they have tackled the first of a long list of basic substances on which our industrial economy is already built. It could put you to sleep During the first decades of its commercial existence, vinyl chloride seemed a most unlikely candidate for the role of heavy in a historic regulatory drama. Put into full-scale U.S. production in 1939, polyvinyl chloride was hailed as a "miracle" material: cheap, stable, fire-resist ant, and able to assume an extraordinary range of soft and hard forms. Its major applications now include coated fabrics (like those used in automobile seat covers), wire insulation, floor tiling, pipe and conduit, phonograph records, and medical supplies, e.g., blood-storage bags. In the beginning the vinyl chloride gas seemed to be virtually harmless. The only apparent dangers were of explosion (at concentrations beginning around 36.000 parts per million) and narcosis. In fact, during the 1940's the gas was tried out as a medical anesthetic, but doctors abandoned it when it was found to cause heart arrhythmia. With low prices providing little incentive for conservation, producers paid no particular attention to workplace exposure levels so long as they were safely below the point of fire and explosion. And yet exposure levels in plants producing the gas itself were probably not very high even in the early years. Vinyl chloride is synthesized from chlorine and petrochemical feedstocks (usually ethylene) in a con tinuous closed process. The plants, which resemble oil refineries (and in some cases are attached to them), are open to the air. Historically, the heavy exposures have occurred in the plants where vinyl chloride is polymer ized into PVC, the whitish powdery resin from which actual plastics are made. It could make you "high" Polymerization is a batch process: vinyl chloride mon omer (VCM) and other substances are put into a pres surized vat, heat is applied, and hours later, when polymerization is completed, the vat is emptied, opened, and cleaned for the next batch. The process is full of leaks. In most of the early plants the gas could be smelled almost constantly (VCM has a faintly sweet odor that seems to be detectable at concentrations above 2,000 parts per million), and workers occasionally got "high" from the fumes. It is widely agreed that in this early period, lasting into the 1950's, exposures of several thousand ppm were common. During the 1950's, as the vinyl industry grew, a trickle of little-noted and often inconclusive medical reports be gan to raise doubts about the monomer's presumed harmlessness. In 1949 a Russian group found a hepatitis like condition in more than one-fourth of seventy-three PVC workers examined, and over the next ten years European researchers encountered other symptoms: skin lesions, a circulatory disorder, gastritis, and derma titis, to name a few. By the mid-1960's these had been confirmed and were described collectively as "vinyl chloride disease." Later in the 1960's, acroosteolvsis, a disease involving a degeneration of the finger bones, was identified among workers who clean polymerization vats. As these findings accumulated, producers began to reduce exposure levels. In 1961 the American Conference of Governmental Industrial Hygienists, a voluntary standards-setting organization, had put the maximum safe exposure at 500 ppm. During the 1960's industry began working to get much lower than that, and by the early 1970's exposure levels were generally in the 100-to200-ppm range, with short-term "excursions" to levels many times higher. In this general downward movement, Dow Chemical BFG65890 s was far and away the leader. In 1961 it had conducted an animal experiment showing liver effects at levels as low as 100 ppm and had decided to get its own plants below 50 ppm. By the early 1970's, Dow had achieved average ex- asures in the neighborhood of 25 Dpm in its copolymer ants (one of which produces resins for Saran Wrap). In 1970, Dr. Pierluigi Viola, an Italian physician study ing acroosteolysis for Solvay, a major European PVC producer, reported an unexpected discovery. After twelve months' exposure at 00,000 ppm. many of his experi mental rats had developed cancers. Doubts about Viola's procedures led Montedison and other European producers to commission Dr. Cesare Maltoni to undertake a largescale animal experiment to see if this carcinogenic effect could be replicated at lower exposure levels. By the end of 1973 Maltoni's well-executed study had shown that levels of VCM as low as 250 ppm induced a variety of cancers in rats, including angiosarcomas of the liver. In June, 1974, he reported angiosarcomas at 50 ppm. American producers began to join the inquiry into vinyl chloride and cancer in 1973. Early that year the Manufac turing Chemists Association decided to commission two massive studies. One was an animal study somewhat like Maltoni's (it has since confirmed his findings). The other was an epidemiological analysis of the morbidity and mortality history of American vinyl workers. In December, Dr. John L. Creech, a Louisville, Kentucky, surgeon who is plant physician for B.F. Goodrich's mas sive PVC installation there, received a report that one of the workers had died of angiosarcoma of the liver. Re membering that another worker had died of the same use two years earlier, he notified a superior. In midJanuary, 1974, while a systematic mortality study of Goodrich workers was being organized, Creech received a report of a third angiosarcoma death. On January 22, B.F. Goodrich announced the three deaths and their cause. To date, a total of eight persons employed at the Louisville plant have been found to have contracted this disease. They blew the whistle themselves As of January, 1974, literally all the information link ing vinyl chloride to cancer had been developed by the industry on its own initiative. As Ralph L. Harding Jr., president of the Society of the Plastics Industry, ob served, "This is a unique situation. Industry financed the studies, and industry blew the whistle on itself." But this was quickly forgotten in the furor that arose during the weeks following B.F. Goodrich's announcement. Within days, regulators, public-health doctors, and union officials had begun to dominate public discussion of the vinyl problem. Within weeks, the Louis ville Times initiated a series of stories alleging that in dustry had engineered a Watergate-style cover-up of the angiosarcoma discovery, which it abandoned only when it saw that the information was about to leak anyway. This charge was symbolic of the manner in which the initiative passed out of the hands of industry. It was seized, rapidly, by a loose but not uncoordinated network of regulatory agencies, government research in stitutes. academic medical teams, labor unions, and other groups united by a common commitment to eradicate en vironmental causes of disease. This "regulatory-medical complex" is largely the creation of a decade's federal legis lation in the medical and environmental fields. Its unoffi cial leader is Dr. Irving J. Selikoff, professor of community medicine at the Mount Sinai School of Medicine in New York City. The one-man power elite White haired, gracious, and preternaturally energetic, Selikoff is best known as the man who explored the haz ards of asbestos and who fought for many years to get them reduced. But a glance at his credentials shows him to hold so many other distinctions and positions that he constitutes a virtual power elite all by himself: a recipient of the Albert Lasker Award of the American Public Health Association, he is also director of Mount Sinai's Environmental Sciences Laboratory, governor and past president of the New York Academy of Sciences, editor in chief of Envitonnuntul Tlcscavcli% president of the So ciety for Occupational and Environmental Health, and consultant to the A.F.L.-C.I.O. as well as to an almost end less list of medical organizations and government insti tutes. He seems personally as well as professionally close to nearly everyone who matters in government occupa tional medicine, and has excellent contacts in the press, which he uses skillfully. Though he insists that he is only a scientist, Selikoff is also a crusader and reformer, and the weapons he takes into battle, aside from his many personal talents, are research and publicity. Within a month of B.F. Goodrich's announcement, half of Selikoff's staff was working on a series of medical and epidemiological studies of workers at three older PVC plants. Researchers from the Harvard School of Public Health began an analysis of morbidity and mor tality in Goodrich's Louisville plant. The National Insti tute of Occupational Safety and Health, which does re search and standards development for OSHA. began a major epidemiological study of workers at four older plants, and together with OSHA sent out numerous teams to conduct "walk-through" inspections of PVT produc tion facilities across the nation. In May, Selikoff con vened in New York City a large international working group on vinyl chloride, held under the auspices of the New York Academy of Sciences. As Dr. Joseph K. Wag oner of NIOSH described the position of the many re searchers who entered the field, " `Seek and ye shall find' is where we're sitting right now." What they found was a great deal of information that linked vinyl chloride ever more closely to a variety of 6 BFG65891 diseases, and this information in turn generated news paper copy. To an attentive reader, the cumulative im pression conveyed was of a hidden crisis slowly uncov ered. With each passing week, the discovery of yet another angiosarcoma case or the release cf a new report seemed to show the crisis to be graver and more wide spread than it had been the week before. The tacit message was that industry had failed, and that govern ment would have to step in and do something fast. Federal regulators were quick to respond. By early February NIOSH and OSHA were actively at work on the problem of workplace exposure. (See the report on page 4 .) By the beginning of April OSHA had issued an emergency temporary standard of 50 ppm and in May it proposed "no detectable level" as a permanent standard. But during the summer, the plastics industry, which had maintained a low profile during the preceding months, reassumed the initiative under the leadership of S.P.I.'s Ralph Harding and Jerome H. Heckman. The burden of the industry position was that OSHA's pro posal was not required on medical grounds and was tech nically and economically unfeasible. In its place S.P.I. advocated a phased reduction to 10 ppm as an average and 25 ppm as a ceiling by 1976. The industry case was set forth in considerable detail and with much documentation during the OSHA hearings that began on June 25. Making policy in a desert It was clear at the hearings that, in the end, the vinyl chloride decision was going to be made in an informa tional desert relieved by only the most occasional oasis of knowledge. It was established that vinyl chloride causes cancer and other diseases. It was also established that, over the course of two decades, industry had re duced exposure levels in its plants by a factor of some thing like 50 without experiencing notable hardship or burdensome expense. But beyond that almost everything was uncertain. One large area of uncertainty concerns the shape of the so-called "dose response" curve for vinyl chloride between 0 and 50 ppm--the range within w'hich, presum ably, OSHA will set the permanent standard. To date, no animal experiments have been completed at exposure levels below 50 ppm, and since historic exposure levels in most existing plants have been above that level, it is ex tremely unlikely that epidemiological studies can reveal anything about human response below the level. The data for Dow Chemical's Midland, Michigan, copolymer plant, where exposures have been monitored for upwards of a decade, are difficult to interpret. Dow's own studies sug gest no adverse health or mortality effects for workers at exposures below 200 ppm; however, Dr. Selikoff's group reports a significant incidence of abnormal symptoms even among Dow workers. Where data are unsatisfactory, one must fall back on inference and theory--but these have proved even less satisfactory, and much more subject to dispute. At the theoretical level, there is disagreement over how cancer is caused. Advocates of the "no detectable level" argued for flic so-called "olie-hif" theory of cancer causation, which holds that there can be no such thing as a risk-free exposure to a carcinogen. The theory implies that any identifiable exposure to vinyl chloride is certain to cause angiosarcoma, at however low a rate. But there is another theory of cancer causation, which emphasizes the role of the body's immune system in com bating cancer. According to this theory, cancers appear when the immune system breaks down. If what a carci nogen does is to weaken the immune system, and if the weakening process requires a certain level of dose, then it is possible that there is a risk-free level of exposure. At the present time, there is no definitive way to evalu ate the truth of these competing models. Thus when OSHA chooses a standard, it will do so in almost total ignorance of the different rates of cancer and other dis eases to be expected at different exposure levels. The cost of approaching zero The agency will be just as uncertain about the other major point in dispute--the level below which it is not economically feasible for industry to reduce exposure. "No detectable level" advocates point to the huge ex posure decreases that industry has already achieved, to the fact that many producers got below 50 ppm soon enough after the emergency standards were issued on April 5, and that not a few were far below that. To many regulators, it seemed obvious that industry could get to a near-zero level if it really wanted to. Industry representatives argued vehemently that a nondetectable level simply could not be attained. "Even a system that doesn't leak, leaks," thundered Todd C. Walker, president of Firestone Plastics, at the OSHA hearings. The companies also argued that efforts to ap proach zero would be extremely expensive. Firestone, for instance, detailed every capital expenditure that would be necessary if it tried to reach "nondetectable" exposure levels and concluded that the total cost would equal the entire value of its existing plant. Even then. Firestone insisted, it would not ultimately achieve a "nondetectable" exposure and would be forced to go out of the plastics business. By the end of the summer, it appeared that even the OSHA staff felt the standard might be unjustified. An August, 1974, report by the agency's Division of Program Evaluation and Research observed: "First, r not clear that it is technically feasible to comply with -he proposed standard without a shutdown of the entir.- . .r vl chloride industry. Second, it is not clear from exist i s. <\perimental and other historical data that a "no deter';n . ..-I-stand ard is justified. And third, it is quite clear . .mpliauee BFG65892 with the proposed standard will require substantia! cap ital investments and lead times." They'd call it a sellout If these findings should lead OSHA to coniproim.-NC- to set an exposure standard of. say, 25 ppm--the agencj should not expect to be praised for its moderation. It may even be assailed for violating its charter. The Occupa tional Safety and Health Act of 1970 states that OSHA, in regulating toxic materials, "shall set the standard which most adequately assures, to the extent feasible, on the basis of the best available evidence, that no employee will suffer material impairment of health or functional capacity even if such employee has regular exposure . . . for the period of his working life." Members of the regulatory-medical complex would surely insist that a compromise was incompatible with these words--and would see it as an unprincipled sellout, sacrificing lives for dollars. Industry, meanwhile, is apt to view whatever level is allowed as an arbitrary interven tion, reflecting political emotionalism rather than reason. And whatever the level, it is hard to believe that the new vinyl chloride standard will do much to end the confusion and uncertainty that currently prevail in many different industries subject to regulatory power. The vinyl chloride hearings have made it clear that practically nobody in government, industry, or labor is willing to discuss these regulatory issues in trade-off terms. "We don't equate lives with dollars and cents--not at the Department of Labor," John Stender, Assistant Secretary of Labor in charge of OSHA, declares. Even spokesmen for industry seem unwilling to chal lenge Stender's formulation head-on. "If we know we're exposing our workers to a known health hazard, we get out of the business," says Dr. Ben Holder of Dow. In the course of the long argument about vinyl chloride stand ards, businessmen have shied away from asserting that some level of mortality might actually be "worth it." In stead, they have tried to smuggle some practical consid erations into the discussion by pointing to problems of "engineering and economic feasibility"--as if feasibility were an absolute. One reason for the general reluctance to think in costbenefit terms is to be found in the language of the Occu pational Safety and Health Act itself. But another rea son lies in the ethos of the regulatory-medical complex, which has something more on its mind than the rate at which people get sick or die. It is committed as well to a larger conception of the good society. In this society the idea of health is central. Ever more remote causes of disease would be eliminated. The role of medicine in this society would be different; it would no longer merely cure, but would actively redesign the environment and ways of living to prevent disease. In evitably, it would be a society in which doctors, by virtue of their expertise, possessed considerable power. The role of markets would be sharply curtailed, inasmuch as they often lead people to make decisions contrary to their best medical interests. In this sense the regulatory-medical complex is a political movement. As such it perceives in issues such as the vinyl chloride standard a symbolic im portance that transcends the particular merits involved. They don't like business And, of course, it is an antibusiness movement in its underlying commitment. American regulatory agencies seem to reflect the times in which they were founded ;the new regulation was established in an era of intense con flict and hostility to business, and there is little prospect of the movement's suddenly acquiring another personali ty. For all its unattractive implications for regulatory equity and consistency, this fact is not entirely without its redeeming aspects. By pressing industry hard, these agen cies will hasten economic modernization. It is clear that they have long since achieved immense success in raising health consciousness in industry and labor alike. As Dr. Ralph Langner, an industrial hygienist at Dow Chemical, says, "Vinyl chloride is to industrial hygiene what Rachel Carson was to the environmentalists." In any case, if Americans are now going to assume the responsibility of deciding what is a "socially acceptable risk," and thus of implicitly putting a price on human life, surely it is desirable that the critical decisions not be left entirely to business--or to any one group or center of authority. A process of indeterminate struggle between business and antibusiness forces, yielding decisions more political than rational, seems preferable to a system in which a single cooperative establishment coolly announces the exact going rate at the close of every business day. Even so, it seems clear that the process of conscious ness-raising could usefully flow in the other direction as well. The regulatory-medical complex would not be any the worse if it had a clearer sense of the novelty of the concept of health it is promulgating and of the uneasiness of its relationship to the existing economic system. And it could take more fully to heart the potential conse quences of its regulatory interventions for ordinary liv ing standards. As G.J. Williams, vice president of Dow Chemical, remarked recently, "You could probably not find a single thing in the world that's essential, but they all go towards making life pleasurable. You can do with out almost anything, but not without everything." END \TED IN U.S A BFG65893 I* Hemangioendothelial Sarcoma of the Liver and Hemochromatosis Edward B. Suasman, MO; Irwin Nydick, MO; George F. Gray, MD, Naw York A patlenl who had idiopathic hemochro- history included a 37-year-old brother with maloaia with cirrhoaia, that waa traatad by adult onset diabetes mellitus and obesity multlpla phlabotomlaa, developed haman- who waa said to have hemochromatosis, gioendoiholial aarcoma (Kuplfar call car- diagnosed after this was established in our coma) ol tha livar with widaapraad bony patient metaataaaa. Tha poaaibla ralationahip ba- A physical examination showed blood twean hemochromatosis, cirrhoaia and pressure, 110/60 mm Hg; fair complexion this rara tumor la discussed. without pigmentation; pretibial edema; splenomegaly; and testicular atrophy. Per tinent laboratory studies disclosed the fol lowing values: hemoglobin, 13.6gm/100 ml; An exceptional instance of heman. gioendothelial Barcoma occurred hematocrit reading, 42.5%; white blood cell count, averaging 3,400 cu mm; platelet in a patient with long-standing idio count, 40,000 cu mm; serum iron, 228pg/100 pathic hemochromatosis. Less than . 100 cases of this rare tumor have been reported in adults.''14 While the cause of this tumor is unknown, many cases have been associated with cirrhosis or the administration of thorium dioxide suspension (Thorotrast). ml; total iron-binding capacity, 228|ig/100 ml; total serum bilirubin, 1.8 mg/100 ml; serum glutamic oxaloacetic transaminase (SCOT), 52 milli-international units/ml (normal, 10 to 50 m-IU/ml); scrum glu tamic pyruvic transaminase (SGPT), 40 units (normal, 5 to 40 units); serum alkaline phosphatase, 5.3 Bodansky units (normal, Report of a Case 1.5 to 5.0); fasting blood glucose, 276 mg/100 ml; and + 4 glycosuria. There was A 46-year-old white man (NYH 77-40-16) no evidence of hemolysis. Electrocardio was admitted to the New York Hospital- grams showed nonspecific S-T segment Cornell Medical Center in July 1968 be and T wave abnormalities. The red blood cause of diabetes, weakness, impotence, cell (RBC) agglutination test for anti pancytopenia, edema, and hcpatospleno- thyroid bodies was positive 1:2,500. Radio megaly. Past medical history included se active iodine uptake in 24 hours was 23%. vere "txphoidal" infectious mononucleosis Percutaneous liver biopsy specimen in 1957, adult onset diabetes mellitus that showed a marked increase in iron deposi was diagnosed in 1964, treated initially tion, especially in periportal hepatocytes with oral hypoglycemica and then insulin, (Fig 1), periportal fibrosis, and glycogen and onset of pancytopenia in 1966. Family vacuolization of hepatocyte nuclei. The diagnosis of idiopathic hemochromatosis complicated by diatwtes mellitus and a Accepted for publication July 30. 1973. From the departments of pathology (Dra. Sues- man and Gray) and medicine (Dr. NydirJt), New York Hoepital-Cornell Medical Center, New York. Reprint requests te 626 E 68th St, New York 10021 (Dr. Gray). diagnosis of hypothyroidism were made. Biweekly phlclmtomics were begun. Two years later, in June 1970, after 63 unita of blood (31,500 ml) had been re moved by phlebotomy, a liver biopey speci men showed that iron store* were still present but greatly decreased in compari son to the original specimen. The amount of iron removed by phlebotomy was esti mated to be 16 mg; however, serum iron was 200pg/l00 ml and total iron-binding capacity was 200pg/100 ml. Over the next three months the patient lost 6 kg, had a low grade fever, and pain in the left upper quadrant, back, and left shoulder. In September 1970, he was read mitted because of multiple pathologic rib fractures. He had developed scleral icterus, lymphadenopathy, and hyperpigmentation of pretibial skin. The serum iron was now 174pg/100 ml and total iron-binding capac ity, 164pg/100 ml. Abnormal liver function was now indicated by the following values: SGOT, 103 m-IU/ml; SGPT, 25 units; alka line phosphatase, 164 m-IU/ml (normal, 30 to 85); and total bilirubin 2.7 mg/100 ml. A biopsy specimen of a soft tissue mass sur rounding a pathologic fracture of the sixth rib on the left side of the chest showed metastatic anaplastic malignant tumor. The only clinical evidence of a primary site was a large defect in the right lobe of the liver demonstrated by a liver scan, but a definite diagnosis was not established. The patient was treated with medroxypro gesterone acetate (Depo-provera), cyclo phosphamide (Cytoxan), prednisone, and radiation therapy to the fracture site. Three months later the patient was ad mitted because of severe generalized hone pain. He had tenderness over multiple ribs, neck vein distention and decreased higher integrative functions. Laboratory data in cluded: serum iron, 122pg'100 ml; total iron-binding capacity, KtOjig/lOO ml; total 6iiirubin, 2.1 mg/100 ml; direct bilirubin, 0.6 mg/100 ml; alkaline phosphatase, 269 m-IU/ml; and negative a-feto globulin. Multiple osteolytic metssuses were seen Aren Psthol/Voi 87, Jan 7874 Hemangloendothellal Sarcoma/Sussman at al 39 BFG65894 f in roentgenograms of ribs, cranial vault, long bones, clavicles, scapula, and pelvis. Liver scan showed hepatospienomegaiy with a grossly irregular distribution of ra dioactivity in the liver. A regimen of duorouracil was added to his therapeutic pro gram but he developed hepatic failure and hypotension and died. The final clinical diagnoses were meta static malignant tumor of unknown pri mary site and hemochromatosis with dia betes mellitus and mild hypothyroidism. Autopsy Findings The liver weighed 1,600 gm and was chocolate-brown with diffuse, firm, 0.3- to 1.0-cm nodules separated yyr-v' by thin bands of connective tissue. <& - . |^': ^fs^j G>< Htfj1- ' ' "i Y f Microscopically, there was a pigmen- I tary cirrhosis with hemosiderin de- I posits at approximately the same I level as seen on the last antemortem Fig 1.--Pretreatment percutaneous liver biopsy showing marked increase in iron dep osition in hepatocytes and Kupffer cells (hematoxytin-eosin, original magnification X400). yjiver biopsy specimen. Glycogen vacu olization of hepatocyte nuclei, bile stasis, and scattered foci of necrosis in regenerating nodules were seen. The pancreas, submandibular glands, and lymph nodes `were also dark brown and the testes and thyroid were atrophic. Iron deposits were most marked in the pancreas, sub mandibular salivary glands, lymph Fig 2.--Hemangloendothellal sarcoma in liver. Hemorrhagic and necrotic mass replac ing a large portion of right lobe of liver. Multiple smaller tumor nodules are scattered throughout remainder of the cirrhotic liver. nodes, zona glomerulosa of the adre nals, choroid plexus of the brain, i 'testes, thyroid, and the kidneys. A largely necrotic and hemorrhagic 11 x 10 X 8-cm tumor was found in the posterior portion of the right lobe of the liver (Fig 2). Multiple 0.5- to 2.0-cm hemorrhagic nodules were scattered throughout the remainder of the right and left lobes of the liver, primarily in and around portal veins. Microscopically, the tumor consisted of large, plump, spindle-shaped cells with large, vesicular nuclei with coarse, clumped chromatin (Fig 3). Mitoses and tumor giant ceils were numerous. Reticulin stains showed that the tumor cells iined anastomos ing vascular channels containing RBC. The tumor dufusely infiltrated between hepatocytes and. in some areas, bore a striking rr-. mblance to hyperplastic KupilVr cods. A few tumor cells contained nomosiderin granules and some ai -o -i.owed eryth- rophagocytosis. Kxiramciuliary hem atopoiesis within the tumor or re maining liver was not seen. Identical 40 Arch Pathol/Vot 97, Jan 1974 Hamangloandothallal Sarcoma - Suasman at al 1 M*J 1 tumor tissue was found in many ribs and adjacent soft tissue, vertebra, and the cranial vault. This lesion was interpreted as being hemangioendothelial sarcoma. There was also cytomegalic inclu sion virus pneumonia of the middle and lower lobes of the right lung. jt Comment Hemangioendotheiial sarccma of 3 the liver is a rare tumor. Only one in stance was found in 52,000 autopsies at the Los Angeles County Hospital1 and this lesion constituted only 3% of primary malignant tumors of the liver at Memorial Hospital for Cancer and Allied Diseases in New York dur ing a 25-year period.1 Less than 100 cases of hemangioendotheiial sar coma of the liver have been reported in adults,1" but the exact number of cases is uncertain because of the pro liferation of names resulting from uncertainty of the celt of origin. Des tv ______________ Fig 3.--Hemangioendotheiial sarcoma consists of muitipis anastomosing vascular channels lined by plump endothelial-like cells with pleomorphic nuclei and bizarre mitot ic figures (hematoxylin-eosin, original magnification x 250). ignations have included hemangio endotheiial sarcoma of the liver, ma lignant vascular tumor of the liver, and prognosis.'*'" In adults, males cluding hepatocellular carcinoma and Kupffer cell sarcoma, hemangioendo are affected approximately three cholangiocarcinoma." The latent pe thelioma, hemangioblastoma, angio times as frequently as females. riod between the administration of sarcoma, endothelioblastoma, reticu- Hemangioendotheiial sarcoma of the thorium dioxide suspension and loendothelioma, angioplastic sarcoma, the liver is a rapidly progressive fatal the clinical onset of hemangioendo primary hepatic sarcoma, angioblas- disease in adults. Clinical findings theiial sarcoma was often as much as tic sarcoma, endothelioma, hemangio- frequently include rapid hepatic en 20 years. Further support for the role sarcoma, and malignant hemangi largement, hemorrhagic ascites and of thorium dioxide suspensions came oma. jaundice. Occasionally, a vascular with the experimental induction of Hemangioendotheiial sarcomas may bruit is heard over the hepatic re this tumor in animals injected with arise in a variety of sites including gion.' Microangiopathic hemolytic colloidal solutions of thorium diox liver, bone, spleen, breast, and subcu anemia* and hypercalcemia' have also ide." Another implicated iatrogenic taneous tissue. The exact primary site been reported in association with thia agent is arsenic, according to a report is sometimes difficult to determine tumor. Distant metastases are pres by Regelson et al" concerning heman because of rapid spread and possible ent in approximatelyT>0% of cases at gioendotheiial sarcoma of the liver in multicentric origin. Hemangioendo- autopsy, most commonly in portal a patient who had received Fowler so ' thelial sarcomas are occasionally dif lymph nodes, lungs, bones, and lution. There was no history of or ficult to distinguish from extremely . spleen. Death may follow intraperito- morphologic evidence of exposure to vascular spindly hepatocellular carci neal hemorrhage secondary to rup either thorium dioxide suspension or nomas or vascular metastases, partic ture of the tumor or from hepatic arsenic in our patient. ularly of adenocarcinoma of the kid coma. Cirrhosis was present in approxi ney -end leiomyosarcoma. The differential diagnosis also includes L Kaposi sarcoma and choriocarcinoma. Two distinct age peaks in the dis Several associations of possible etiologic importance have been noted with these tumors. MacMahon et al" reported the development of this tu mately one third of the reported adult cases of hemangioendotheiial sar coma of the liver." The types of cir rhosis included alcoholic, postnecrotic, tribution of the reporled cases of mor after the administration of a tho and pigmentary. Ansari and tVci- - hemangioendotheiial sarcoma of the liver have been noted by Videbeck,' fone at 8 months and the other at 49 rium dioxide suspension, and Da Silva Horta et al1* found 22 cases of heman gioendothelioma in 1,107 patients gent* have explained the association of cirrhosis and hemangioendotheiial sarcoma of the liver in two ways: one, Lycurs. The tumor in infants is differ exposed to a thorium dioxide suspen that cirrhosis plays a role in the gen ent from that seen in adults in clini sion. This suspension is also associ esis of this tumor as it docs in hepato cal and morphologic presentation. ated with other malignant tumora in cellular carcinoma; two, that the tu Arcft PatluX/Vol 97, Jan 1974 BFG65896 Hemangioendotheiial 8arcoma/Suasman at al 41 ** mor itself may initiate fibrosis and nodular regeneration. The latter ex planation seems less likely, since in cases like the one reported here, dif fuse cirrhosis was demonstrated prior to any evidence of existence of the tu mor. Only two cases of hemangioendothelial sarcoma in hemochromatosis have been previously reported.*, In one instance," hemochromatosis was suspected only at autopsy because of pigmentary cirrhosis and iron deposi tion in pancreatic acini; however, other causes of hemosiderosis were not ruled out clinically and iron was not identified within tumor cells. In the second instance," the antemortem diagnosis of pigmentary cirrhosis was made only a few weeks before death and was not treated. Iron was found in many of the tumor cells. In three of the four cases of hemangioendothelio ma of the liver reported by Alpert and Benisch," hepatic siderosis was noted and the authors suspected that this was a consequence of micro angiopathic hemolytic anemia due to the tumor. In tho case reported here, the pres tosis of it thorium dioxide suspctiHion ence of diabetes 1V4 years before he and hemosiderin by tumor cells mim mochromatosis was diagnosed, sug ics the activity of KupIFer cells, but gests that the latter condition may docs not prove Kupffer cel! origin, have been present at least four years , since other tumors may demonstrate antemortem. The patient was treated phagocytic activity including eryth- with multiple phlebotomies that re rophagocytosis. The significance of sulted in decreasing serum iron levels extramedullary hematopoiesis within and diminution of liver iron load as the tumor is unknown. seen on the biopsy specimen. Never Many of the clinical features seen theless, he went on to develop a in patients with hemangioendothelial hcmangiocndothelial sarcoma of the sarcoma of the liver are shared with liver, a situation analogous to an in patients having hepatocellular carci stance of hepatoma arising in treated noma. Because of the extremely vas hemochromatosis as reported by cular nature of this tumor, aspiration Hines et al." It would, therefore, ap or popdle biopsy is contraindicated pear that the removal of iron does not and may result in fatal hemorrhage. prevent the development of either Early diagnosis and partial hcpatcc- hepatoma or hemangioendothelial tomy might offer some hope of in sarcoma once cirrhosis has developed. creased survival but unfortunately KupfTer cell origin of these tumors nearly all lesions in adults are diag is suggested by the tendency to form nosed at an advanced stage and char anastomosing vascular elements acterized by a rapidly progressive lined by prominent endothelial-like course leading to death within six cells. The presence of hyperplastic months. Kupffer ceils in areas of the liver re mote from frank tumor as described by Baker et al* also supports a Kupf Nonproprietary Name and Trademark of Drug fer cell origin of this'tumor. Phagocy Fluorouscii-i^'iufcc, Fluoroplex. References 1. Edmondson HA: Tumon of the Liver and liver. J Pathol 72:173-182, 1956. Intrahcpatic Bile Duett. Atlas of Tumor Pathol 9. Kwitten J, Tartow LR: Hacmoehromatosis ogy aeries. Washington, DC, Armed Forces insti snd Kupffer-cell sarcoma with unusual local tute of Pathology, 1868, section 7, pt 25, p 139. isation of iron. J Pathol 92671-673,1966. 2. Adam YG, Huvoi AG, Hajdu SI: Malignant 10. Buraton J: Kupffer cell sarcoma. Cancer vascular tumon of the liver. Ann Surf 176:376- 11*708.8112. 1QR8 383, 1972. 11. Galup LN, Hawkins RA, Manalo-Estrella 3. Videbeck A: Hemangioendothelioma of tho P: KupfTer cell sarcoma of the liver. Aeroep Med liver. Ada Patdiatr Scand 33:129-143, 1946. 36:988-989, 1965. 4. Ansari A, Weigent CE: Hemsngiocndothe- , 12. Miller EA, Richard WG, Reed WH: lial sarcoma of the liver. Am J Gaetrventerei Hacmangioendotheliai sarcoma at the1 liver 66:420-427, 1971. (Kupffer-cell sarcoma). IPis Med J 63:471-476, 5. H astings J R: Malignant haemangioendothe- 1964. lioma (hacmangioblastoma) of the liver. J Pathol 13. Blackwell JB, Joeke RA: Kupffer cell sar 61:49-53, 1949. coma. Am J Dig Die 16:133-138. 1970. 6. Alpert LI, Benisch B: Hemangioendothelio 14. Swarm RL (ed): Distribution, retention ma of iiver associated with microangiopathic he and late effects of thorium dioxide. Ann NY molytic anemia: Report of four cases. Am J Med dead Sei 146:525-868, 1967. 48:624-628, 1970. 16. McGahon JJ, ct al: Solitary infantile 7. Case records of tho Massachusetts General hemangioendothelioma of the liver Report of Hospital (Case 12,1967). N Engl J Med 276.629- one case. Rocky Mt Med J 61:38-39, 1964. 634, 1967. 16. Blumfeld TA, Flemming ID, Johnson WW: 8. Baker H dsC, PagetGE, Davison J: Haeman- Hemangioendothelioma of the liver Report at a gioendotheiioma (Kupffer coll sarcoma) of tho case and review of the literature. Gsaesr 24668- 867, 1969. 17. Edmondson HA: Differential diagnosis of tumors and tumor-like lesions of liver in infancy and childhood. Am J Die Child 91:168-186.1956. 18. MaeMahon HE, Murphy AS, Bates Ml: En dothelial-cell sarcoma of the liver following Thorotmat injections. Am. J Pathol 23:585-611,1947. 19. Da Silva Horta J, et al: Malignancy and other late effects following administration of Thorotrast. Lancet 2:201-205, 1965. 20. Swarm RL, Miller E, Michclitch HJ: Malig nant vascular tumon in nbbits injected intrave nously with colloidal thorium dioxide. Pathol Mu crohiot (Basel) 25:27-44, 1962. 21. Regelson W, et al: Hemangioendothelial sarcoma of the liver from chronic arsenic intoxi cation by Fowler's solution. Cancer 21:614-622, 1968. 22. Hines C, Dsvis D, Ferrsnte WA: Hepa toma developing in hemochromatosis in spite of adequate treatment by multiple phlebotomies. Am J Dig Dio 16649-866,1971, 42 Arch Pathot/Vol 97, Jan 1974 Hamangloandothaiial Sarcoma/Sussman at al BFG65897