Document 2YK8OygMqr5kXrv7d9M6DMoa

V. M. Smith 1. V. Smith June 13, 1974 Vinyl Chloride Disease Allentown Labe Safety net E. Blades B. Watson/J. Novak C. Mantal (received a eopy S/12/74) AtCached la the latest published Informatics Issued by the American Medical Association In their Journal of June 10, 1974. Please note the possibility of persat/ehlld transmission. Should e transmission of this type be possible a vhola new sorld of In vestigation sill have to be provided; this grossly increases the seriousness of the VC problsm. HVS dhd enclosure AP00013902 Medical News How hazardous to health is vinyl chloride? In the months since John L. Creech, MD, asso ciated four deaths from the rare angiosarcoma of the liver with exposure to vinyl chloride In the Kentucky polymerization plant of B.F. Goodrich Co., both the Food & Drug Administration and the Environmental Protection Agency have urged makers of aerosols propelled by vinyl chloride to withdraw them from the market as potentially hazardous. Just how dangerous the ubiquitous plastic in gredient is became clear last month at a confer ence held by the New York Academy of Sciences with American Cancer Society support. During the sessions in New York City, epidemiologists, pathologists, and oncologists from the United States, West Germany, Italy, Romania, and Japan reported on studies that showed: e Those at risk of liver damage are not just the estimated 6,500 workers (in the United States alone) who produce the polyvinyl chloride poly mer from the vinyl chloride monomer. Thousands of other workers are also at risk--those who work in warehouses where the resin is stored, and those who work in plants where the polymer is heated before being used to make tiles, contain ers, and other products. Vinyl chloride disease, as it is now fast be coming known, is not limited to the liver. Inhaling the fumes can damage pulmonary function, pro duce thrombocytopenia, enlarge the spleen and lead to excessive production of immature eryth rocytes. Handling vinyl chloride can produce acroosteolysis in the fingers and Reynaud phenomenon in the hands. Exposure to aerosols containing 50 to 10,000 ppm of vinyl chloride can regularly induce tumors in rats, mice, and hamsters--not only in the liver but in other tissues as well. The usual battery of liver function tests cannot be relied upon to detect the periportal fibrosis that precedes sarcoma growth. The liver does not return to normal for up to 2V6 years after a polyvinyl chloride worker changes jobs and is removed from exposure. HanB Popper, MD, the Mt. Sinai Hospital pathologist who is now a visiting fellow at the National Institutes of Health, told the New York meeting that the fibrosis and tumors induced in tlio polyvinyl chloride workers is virtually iden tical to the disease suffered by German vineyard laborers as a result of exposure to inorganic atonic sprays. His studios of liver biopsies from i'v imticntft currently under treatment fur hepatic anrinsaronma show "widespread activation of hepatocytes and de-differentiation of fibroblasts consistent with pre-malignant changes in liver tissue far removed from the primary tumor." (Dr. Creech said in an interview that both patients un dergoing chemotherapy for their angiosarcoma have shown improvement.) Dr. Popper said he has no doubt that one or more of the compounds involved in the production of vinyl chloride and its resin polymer are specific carcinogens. On the epidemiologic front, Clark W. Heath, Jr., MD, of the Center for Disease Control in Atlanta told a press conference that J,3 cases of hepatic angiosarcoma have now been traced to 4 American polyvinyl chloride plants. One British case and two German cases have also been documented. These cases, except for the two now under treatment, were found through retrospective in vestigations, and after an average exposure of 12 years, Dr. Heath said. Furthermore, one child of || an angiosarcoma patient has developed a primary l| hepatoma. Concerned Manufacturers Chemical industry representatives at the con ference made it clear that they were taking the matter very seriously. The companies have in stituted, in some cases, detection warning systems to alert workers to don respirators in case of dangerous concentrations of vinyl chloride. (That is, concentrations of more than 50 ppm.) Maurice N. Johnson, MD, head physician at Goodrich, said his company has now reduced general levels of the chemical in the air of the plants to about 15 ppm. The National Institute of Occupational Safety and Health (NIOSH) has called for levels of loss than 1 ppm of vinyl chloride. The levels in the Goodrich plants fall short of this, but the reduc tion could still reduce the danger, according to Cesare Maltoni, MD, of the University of Bologna, Italy. Dr. Maltoni first called attention to tumor induction by the chemical in the fall of 1972 in reports presented to the Italian government and industry, and to representatives of the Manufac turing Chemists Association of the United States. Dr. Maltoni's first reports were based on the studies where rats were administered nerosolinized vinyl chloride. The Italian oncologist is pres ently conducting year-long rat exposure tests at 10 and 25 ppm in an attempt to determine the limits of dose-related carcinogenesis, lie said that in one trial, animals that wore exposed to 50 ppm continued on page t.ir> f JAMA. June 10. 1674 Vol 228, No 11 Medical News 1355 AP00013903 Vinyl chloride symposium continued from page 1355 for four months and then observed for eight more months developed 75^ fewer tumors in compar ison to animals exposed for an entire year. This would at least offer some hope that vinyl chloride and polyvinyl chloride workers whose exposure is now minimised may not develop the liver cancer. Descriptions of vinyl chloride disease came from researchers at the University of Bonn, West Germany, and were, except for the thrombo cytopenia, in a very recent survey of 354 workers (including death certificates of 24) at the Good year Tire & Rubber Co. plant in Niagara Falls. Irving J. Solikoff, MD, of the 5ft. Sinai School of Medicine, who led the investigation of asbestos fiber pathology a few years ago, headed the Mt Sinai team that made the Niagara Falls check. Dr. Sclikoff, conference co-chairman with E. Cujier Hammond, ScD, vice president of the American Cancer Society, said the platelet loss might also have been confirmed with better equipment. Albert Miller, MD, of the Mt. Sinai team re ported that 80 To of the Goodyear workers showed some evidence of pulmonary obstructive disease after 20 years of exposure to vinyl chloride fumes regardless of cigarette smoking history. At Louisville, Dr. Creech has attempted a con trolled study. He included all Goodrich workers . continued on next page Medical News 1303 Medical News continued from previous page in an SMA-12 biochemical survey, screening both office workers and butadiene rubber workers along with those exposed to vinyl chloride. Dr. Creech, who first noticed acro-osteolysis in poly* vinyl chloride workers in 1964, found no sig nificant changes in the serum levels of lactic dehydrogenase, alkaline phosphatase, bilirubin, or SGOT--even in workers who had been heavily exposed over some time. There were some changes, though: 66% of the workers, compared with 0.02% of a general hospital population sample, had elevated levels of factor IV of lactic dehydro genase. Those workers who twice showed any abnormality on the SMA 12 screening were sub jected to technetium liver scans and angiography, followed by transjugular vein biopsy when a tumor was indicated. This was done in 16 cases--and 2 of the work ers had angiosarcomas. Dr, Creech said that an giography showed a 20-second "blush" around the tumor in the sarcomas. In his previous ex perience with hepatic metaatasea from extrahepatic primary cancers, he added, angiographic blushes persisted only about Ave seconds. Persistent Liver Damage Paul D. Berk, MD, of the National Institute of Arthritis, Metabolic and Digestive Diseases presented the bad tidings of the persistence of liver damage. He described the case of a 27-yearold man who worked 5Y2 years as a reactor cleaner in Goodrich's vinyl chloride, polymerization unit In Louisville. When he complained of fever and weight loss, he was found to have an enlarged spleen and liver and slight elevations in SGOT and serum bilirubin. Three months later he was hospitalized for what appeared to be acute hepa titis. During those three months he had been on sick leave and had not been exposed to vinyl chloride. A laparatomy was performed during convalescence, his spleen was removed and a bi opsy showed surface fine nodularity and fibrosis in the portal region of his liver. He also had proliferation of bile duct cells and activation of sinus lining cells. He went back to work, but since environmental toxicity was suspected, the new job was far from the vinyl chloride polymerization area. This was long before the reports linking cancer and vinyl chloride; but after these reports, Dr. Creech re ferred the patient to NIH. By then 2\' years had passed since the hepatitis-like episode. The man's liver function tests and liver scan were normal, But, according to Dr. Berk, a bi opsy showed the liver was stilt covered with ricc- 1364 JAMA, June 10, 1974 Vol 226. No 11 grain-sized nodules and the portal fibrosis was still strongly in evidence. In addition, the NIH pathologists saw some bridging between portal areas and hepatic veins, and hepatic vein cath eterization revealed a 12 mm Hg wedge pressure. In an effort to find a diagnostic test, NIH re searchers tried radioactively labeled bilirubin elimination, BSP and indocyanine green clear ance. All appeared normal. Only an experimental bile add clearance test proved abnormal, at least raising some hope of a screening test for vinyl chloride hepatic fibrosis. Meanwhile, Dr. Joseph K. Wagoner, SD Hyg, NIOSH, told reporters of the start of a major prospective-retrospective study of polyvinyl chlo ride workers in six major US chemical plants. This study should eventually include 3,000 per sons exposed in the manufacture of vinyl chlo ride, in the polymerization process and during storage of the resin. Hopefully, it may clarify both the length of exposure required to produce disease. The occurrence of seemingly excess deaths from lymphomas and certain other cancers among the 24 Niagara Falls workers whose death certificates were examined by the Mt. Sinai group. The Germans provided some ominous data on the length of exposure required to produce dis ease. HJ. Marsteller, MD, and colleagues at the University of Bonn have performed extensive peritoneoscopy on exposed polyvinyl chloride work ers. They found one patient with a marked lesion on the surface of the liver after only 2Vi years work in a polyvinyl chloride plant This patient was awaiting biopsy, but in Dr. Marsteller's words "The lesion looks very much like an angio sarcoma." Spokesmen for the Rubber, Cork, Li noleum & Plastic Workers, AFL-CIO, thus may have reason to complain over delays in government regulation of polyvinyl chloride exposure. Public awareness of Pap test A small piece of good news for a change: more women than ever are aware of the Pap smear test and more are having it performed. The American Cancer Society recently reported the results of a Gallup poll, which showed that 87% of women surveyed are aware the test exists, up from 78% in 1963. Better still, 78% of the respondents in the current survey have had the test, up from 48%; and best of all, G2% said they have had a Pap smear within the past 12 months. In 1963, the figure was only 23%. Justin J. Stein, MD. president of the ACS, said these increases indicate that the society's goal of a Pap smear for all women at risk by 197C "is mow realistic than many of us dared hope." Medical News AP000I3905