Document YDqNVR2mZ5n5yQQRGJEnm2NGn

INTER COMPANY AND OFFICE CORRESPONDENCE la subjbct: James T. McCrory H, A. Peed Paul Josenhans David Weinstein Henry Schmidt American Medical Association Journal - VCM DAT* June 12, 1974 won,' A. S. Cunrnin DivjDttr Technical Division addabss: New York, New York TELEPHONE: 4158 Attached for your information is a copy of an article which appeared in the June 10th issue of the AMAJ, The article sunmarizes many of the papers delivered at the recent N. Y. Academy of Science meeting on Vinyl Chloride as well as giving some insight into the on-going studies of NIOSH/Sellikoff and Creech. ASC/vbd 007176 w Medical News turn with S. Leeson, Ihrfsion of mnt Comtonqr on Medicine, circulating cr. spleen. ed a sigtreatment ition into ells. This roup. Dr. nt, inde test, s of imlificantly pnificant usitivity ain teat a. ton, acowerful iponae." nic an. `ng re- ge ia urvival ine in- duraof the i "for npari`g ex- Nowb How hazardous to health is vinyl chloride? In the ""*> 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: Those at ride of liver damage are not just the estimated 6,600 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 60 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 2% years after a polyvinyl chloride worker changes jobs and is removed from exposure. Hans 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 the polyvinyl chloride workers is virtually iden tical to the disease suffered by German vineyard laborers as a result of exposure to inorganic arsenic sprays. His studies of liver biopsies from two patients currently under treatment for hepatic angiosarcoma show "widespread activation of JAMA June 10, 1974 Vot 228, No 11 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 IS cases of hepatic angiosarcoma have now been traced to 4 American polyvinyl chloride plants. One British ease 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 hepatoma. Concerned Manufacturers Chemical industry representatives at the con ference made it dear 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 60 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 16 ppm. The National Institute of Occupational Safety and Health (NIOSH) has called for levels of less 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 aerosolinized 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. He said that in one trial, animals that were exposed to 50 ppm continued on page 1363 Medical News 1355 BOR 007X77 adiology, irofesaor told the res* and i-uterine lisorders umerous Today's >nal and ins: both s." artment Texas, ostltute, mes and d tract n civiline indipoint of ion dur- :al News t* Medical News Irradiation patients get thyroid cancer check An extensive campaign is underway to find the g 000 patif"tff given radiation therapy for ton sillitis between 1938 and 1955 at the Michael fly... Hospital and Medical Center, in Chicago. The recall was prompted by increasing reports of radiation-associated thyroid carcinomas in pa tients who had been irradiated during childhood for thymic enlargement, recurrent tonsillitis, acne, snd impetigo (JAMA 225:487 [July 30] 1973). Radiation therapy for these conditions is no longer in vogue. However, from the 1930s to 1950s the delayed effects of radiation were not ap parent, and hundreds of thousands of patients around the world probably received the treatment, Louis M. Sherwood, MD, chairman of the De partment of Medicine, told Medical News. With the problem now in focus, '`it was deemed essential to reach these people and not ignore the possible risk. We made a commitment to find and evaluate former Michael Reese patients free of charge," Dr. Sherwood said. A staff of secretaries under Margaret Arnold, RN, examined the radiation therapy files and sent letters to all patients at risk. When announcements of the search appeared in Chicago newspapers in March, the hospital switchboard was jammed. In one week nearly 6,000 calls were taken from pa tients treated at Michael Reese and other facilities. Since the program began in January "we have seen .about 700 patients, and many more are scheduled," Dr. Sherwood said. The patients are seen by an endocrinologist who discusses the prob lem and explains the laboratory procedures. Thy roid function tests and a rapid, small-dose scan are done. Two endocrinologists perform the examinations independently to avoid bias, Dr. Sherwood ex plained. The physicians confer and compare their results to the scan. If there is any disagreement, the patient is reexamined by both physicians. The same day, the results are discussed with the patient, and in his presence a phone call is made to his private physician. A follow-up letter includes test results and recommendations for treatment. If all tests are normal, the patient will be seen annually for an indeterminate number of years, Dr. Sherwood said. So far, the incidence of abnormalities in thyroid cans or physical examinations is 15% to 20%, but the number of tumors is unknown. It is too e*r'y to make a definitive statement, he stressed. in addition to the benefits to the individual, JAMA, June 10, 1974 Vol 228, No 11 the program will yield important scientific inform mation about the relationship of irradiation to thyroid disease. Hopefully, the results will lead to methods of preventing thyroid tumors, a bet ter understanding of irradiation risks, and bio chemical differentiation between patients at risk and normals. At present, one group of normal-scan patients are taking thyroid hormone to see whether this will have any effect on subsequent development of nodules. The results will be compared to a ^ group of matched controls. A good follow-up is'" essential, with cooperation between hospitals and physicians throughout the country. Dr. Sherwood said. The program is expensive, costing the hospital 56,000 to $6,000 a week ($60 per patient) for laboratory tests alone. The yearly cost is estimated at several hundred thousand dollars, he said. The program is being conducted by Lawrence Frohman, MD, head of the divisions of endocri nology and metabolism; Martin Cohnan, MD, as sociate director of radiation therapy, and Steven Pinsky, MD, head of the Division of Nuclear Medicine. Vinyl chloride symposium continued from page 1S5S 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 minimized 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. Selikoff, MD, of the Mt. 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. Selikoff, conference co-chairman with E. Cuyler 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% 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 1363 BOR 007178 Medical News continued from previous peg* in w SMA-12 biochemical survey, screening both office workers and butadiene rubber workers along with those exposed to vinyl chloride. Or. Creech, who first noticed acro-osteolysis in poly vinyl chloride workers in 1964, found no aig' nificaat 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 Victor 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 eases^--and 2 of the work ers bad 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 metastases from extrahepatic primary cancers, he added, angiographic blushes persisted only about five seconds. 'x 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 5% years as a reactor cleaner in Goodrich's vinyl chloride polymerisation unit in Louisville. When be 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 bad. 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 2Vi 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 still covered with rice- 1364 JAMA, June 10. 1974 Vo) 228, No 11 , irL /; . grain-sized nodules and the portal fibrosis w: still strongly in evidence. In addition, the NL pathologists saw some bridging between port areas and hepatic veins, and hepatic vein catl eterization revealed a 12 mm Hg wedge pressun In an effort to find a diagnostic test, NIH re searchers tried radioactively labeled bilirubi elimination, BSP and indocyanine green clear ance. AH appeared normal. Only an experiments bile acid clearance test proved abnormal, at leas raising some hope of a screening test for viny 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 ML 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 2% yean 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 s 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, 62% said they have had a Pap smear within the peat 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 1976 "is more realistic than many of us dared hope." Medical News BOR 007X79