Document 5Dvre60OZogEbxYJGxNMg5NE5

CMm CHEMICAL MANUFACTURERS ASSOCIATION August 15, 1994 Dear Vinyl Chloride Health Committee Members: The American Cancer Society's response to our August 1, 1994 letter is enclosed. The response is very favorable and you may want to consider sharing it with your legal departments. Dr. Heath's opinion as the Vice President of the Epidemiology and Statistics Department of the American Cancer Society would add considerable weight to the industry position. I am looking forward to speaking with you on September 9 at 3:00 p.m., EDT. If you have any questions, please call me at (202) 887-1192. Sincerely Enclosure Hasmukh C. Shah, Ph.D. Manager, Vinyl Chloride Panel R & S 147547 2501 M Street. NW, Washington, DC 20037 Telephone 202-887-1100 Fax 202-887-1237 c9 &J Responsible Care ` A Public Commitment AMERICAN VCANCER ? SOCIETY NATIONAL HOME OFFICE CLARK W. HEATH, JR., MD Vice President Epidemiology and Statistics August 4, 1994 Hasmukh C. Shah, Ph.D. Manager, Vinyl Chloride Panel Chemical Manufacturers Association 2501 M Street, N.W. Washington, DC 20037 Dear Dr. Shah: Thank you for your recent letter. The Time magazine chart is certainly misleading. It may well be that the American Cancer Society source they are citing is Cancer Facts and Figures 1994, in which case it is unfortunate that they ignore the word "possible". Cancer Facts and Figures is widely quoted and not infrequently quotations are not entirely accurate. We review the Cancer Facts and Figures text and update the numbers each year and shall certainly take your comments into consideration. There are, of course, many degrees of "possible" when considering risk factors, and in the instance of lymphoma I would think there is a distinctively lower possibility for vinyl chloride than for herbicides, neither being proven. The document is not meant, of course, to be an exhaustive treatise on all possible cause factors at each cancer site, but to provide brief overviews of major points. For no site other than liver (angiosarcoma) is vinyl chloride evidence conclusive, and even there it concerns only high, repeated, occupational exposures to vinyl chloride monomer (ideally, we should distinguish between monomer and polymer). Again, thanks for your letter and its attachments. Sincerely, Clark W. Heath, Jr., M.D. cc: S. Montgomery A. Stone J. Laszlo, M.D. Ft&s 147548 1599 CLIFTON ROAD, N.E., ATLANTA, GA 30329-4251 * 404-329-7686 * FAX 404-325-1467 CH0/OCAL MANUFACTURES ASSOCIATION August 1, 1994 Clark Heath Jr., M.D. Vice-President for Epidemiology and Surveillance American Cancer Society 1599 Clifton Rd. NE Atlanta, GA 30329-4251 Dear Dr. Heath: I am writing this letter on behalf of the Chemical Manufacturers Association Vinyl Chloride Panel to express our concerns regarding a statement in the first full sentence of page fifteen of the ACS publication Cancer Facts and Figures 1994 (as well as in earlier issues). Referring to the risk factors associated with malignant lymphoma, this statement reads as follows: "Other possible risk factors include exposures to herbicides, industrial solvents, and vinyl chloride." We believe that a misunderstanding of this statement may have lead to the association of vinyl chloride exposure with risk of lymphoma in an article by J. Madeleine Nash in the April 25, 1994 issue of TIMS magazine (page 60). A copy of this page is enclosed. The description in the table entitled "The Big Killers" implies, we believe, that vinyl chloride is a "proven" rather than a "possible" risk factor for malignant lymphoma. We are concerned that others may similarly misinterpret the statement appearing in Cancer Facts and Figures 1994. A large number of epidemiologic studies have been conducted on . well-defined occupational cohorts with potential exposure to vinyl chloride. In some of these studies an elevation in lymphoma mortality was observed, but not in others. The largest and most recent such study, published by Wong et al. in 1991, did not observe any excess of lymphatic or hematopoietic cancer deaths, even among workers who were first exposed prior to 1950. In contrast, mortality due to cancer of the liver, with which vinyl chloride exposure is certainly causally associated, was most elevated in the subcohort of workers exposed prior to 1950. We believe that the epidemiologic evidence does not lead to an inference of a causal association between vinyl chloride exposure and ma1ignant lymphoma. V Our view is consistent with that of Sir Richard Doll, who reviewed the evidence in 1988. We note that Doll refers to the studies by Tabershaw and Gaffey (1974) and Waxweiler et al. (1976) as having raised the possibility of an association between vinyl chloride and lymphoma. We hasten to point out that these were early studies conducted on workers who were eventually included in the much larger cohort studies by Wong et al. and referred to in this letter. 2501 M Street, NW, Wasftnqton. DC 20037 Telephone 202-887-1100 Fax 202-887-1237 A Re^JOnstbteCare' II A Public Commitment 'r August 1, 1994 Page 2 We respectfully request that the statement is Cancer Facts and Figures 1994 be amended to better reflect the current state of knowledge about the suspected association of vinyl chloride exposure with lymphoma. The suggested wording to be added is (underlined and in Italics): "Other possible risk factors include exposures to herbicides, industrial solvents, and vinyl chloride, although the evidence supporting an association with vinyl chloride exposure Is limited," An alternative to this change of wording would be to remove the specific reference to vinyl chloride from the statement. We note that vinyl chloride is not mentioned specifically as a possible risk factor for cancer of the lung, although there is also equivocal epidemiologic evidence for an association between vinyl chloride exposure and this type of malignancy. We feel that our suggestion encompasses the current state of the evidence concerning vinyl chloride and lymphoma and would minimize the possibility for the kind of misinterpretation we observed in the TIME magazine article. At the same time, we wish to point out that this letter was intended solely to address possible misinterpretations with respect to lymphoma and vinyl chloride. In no way do we acknowledge the existence of any association between exposure to herbicides or industrial solvents and the occurrence of malignant lymphoma. We trust that this letter and the attachments will serve to provide you with a comprehensive view of the evidence concerning the health effects of vinyl chloride exposure in humans. If you have any questions or would like more Information, please contact me at (202) 887-1192. Sincerely, Enclosures Hasmukh C. Shah, Ph.D. Manager, Vinyl Chloride Panel R&S147550 August 1, 1994 Page 3 References Cited and Enclosed: American Cancer Society. Cancer Facts and Figures, 1994; 1-28. Doll R. Effects of exposure to vinyl chloride. An assessment of the evidence. Scand J Work Environ Health 1988;14:61-78. Nash JM. Stopping Cancer in its Tracks. TIME Magazine 1994; April 25: 54-61. Tabershaw IR and Gaffey WR. Mortality study of workers in the manufacture of vinyl chloride and its polymers. J Occup Med 1974;16:509-18. Waxweiler RJ et al. Neoplastic risk among workers exposed to vinyl chloride. Ann NY Acad Sci 1976;271:40-48. Wong 0 et al. An industry-wide epidemiologic study of vinyl chloride workers, 1942-1982. Am J Ind Med 1991;20:317-34. malfunctions. When she introduced a nor mal nm23 gene (nm stands for non metastatic) into highly malignant human breast cells, then injected these cells into mice, their tendency to form metastases dropped as much as 90%. GUARDING THE MASTER SWITCH Until last week, p53, the subject of some 1.000 scien tific papers in 1993 alone, was considered the most important cancer gene. The jour nal Science even named it Molecule of the Year. But now there is a new contender for notoriety-Krrsi, as Alexander Kamb and his colleagues refer to the multiple tumor- suppressor gene they have just discovered. "Multiple" refers to the fact that defects in this gene can cause many kinds of cancer, including melanoma, lung, breast and brain JACK SWEPSTON, 48. Pancreatic Cancer. On Match 31 this Dallas dentist trav eled to the National Cancer Institute in Bethesda, Maryland, to receive a new type of anticancer vaccine. Prepared by a team of researchers, including Drs. David Carbone and John Minna of the University of Texas Southwestern Med tumors. In fact, functional copies of mtsi may be missing in more than 50% of all hu man cancers. What makes mtsi so significant is its dear role in the cell-division cyde. A cell di ical Center, the vaccine was a synthetic version of a mutant protein fragment vides not at will but in response to specific found in Swepston's tumor. The hope is that the immune system will leam to recognize this target and destroy the cells that make it "I haven't felt a signifi cant improvement yet" he says, "but the doctors are tremendously excited," signals, such as growth factors produced by white blood cells rushing to repair a wound. These signals are picked up by re ceptors on the membrane of the cell and passed along--like batons in a high-speed enues of escape. Not all the myriad cells ulate new areas. But while an embryonic cell relay--through the interior, all the way to a shed by tumors survive the turbulent voy stops proliferating and matures into adult master "on" switch positioned deep in the age through the bloodstream, notes exper tissue, the cancer cells just keep dividing. nudeus. Not surprisingly, many onco ^Jmimeental oncologist Ann Chambers of the One reason for the difference may lie in genes, induding one called ras, the first mdon Regional Cancer Centre in On- a gene known as nm23, first identified by human cancer gene ever identified, are in o. But those that do eventually slip Steeg in 1988. It seems to help mature cells volved in this type of signaling pathway. through blood-vessel walls with ease. Using stop dividing and arrange themselves in an But there are other molecules that deter a video camera attached to a microscopic orderly fashion. Steeg's research suggests mine whether the cell should heed these lens. Chambers has watched in wonder as that in cancer cells this crucial gene often signals. And the small protein produced by melanoma and breast-cancer cells, injected into mice, become lodged in capillary walls, then crawl out into the liver. Three days later, her camera resolves the spidery shapes of tiny metastatic growths. The les son, Chambers believes, is depressingly clear. Cancer cells zip in and out of blood THE BIG KILLERS Estimates in the U.S.. 1994 Cancel Deaths Five-year survival New cases rate lint 153,000 172,000 13% Risk Factors Cigarette smoking.- exposure to asbestos, chemicals, radiation, radon vessels so readily that, once angiogenesis occurs, they should be presumed to have al ready spread around the body. Metastasis is an event of awesome com plexity, one that requires multiple genes to Female Breast Prostate 58% 46,000 182,000 79% 77% Fair'y history: high-fat. tow-fiber diet Age; family history; no pregnancies; lata menopause; early menarche Age: family history, possibly fat intake cooperate as closely as musicians in an or chestra. Some ofthese genes code for chem ical solvents that enable the advancing cell to dissolve surrounding tissue. Others order fittcrtts 25,900 lymphoma . 22,750 Non-Hodgkin s 27,000 3% 52,900 78% 52% ABrsmoking; fat intake Reduced immune function: exposure to herbicides, solvents, vinyl chloride up the production of adhesion molecules that, like treads under a tank, move the cell 19,100 28,600 38% Genetic abnormalities; exposure to ionizing radiation, chemicals: viruses forward. Why would genes do that? The an swer, notes Patricia Steeg of the National Cancer Institute, is that while the genes im Ovary . Kidney 13,600 24,000 39% 11,300 . 27,600 55% Age. family history, genetic disorders, no pregnancies Smoking ........... portant to metastasis are abnormally turned on. they are not necessarily abnormal them Bladder 10,600 51,200 79% Smoking selves. A cancer cell, in many wavs, is not that different from an embryonic cell on its ^lvav to becoming a patch of skin or a bundle f nerves. Both embryonic and cancer cells dA ivide and form ill-defined clumps. Both get up and move around. Both migrate and pop Uterus <***' Endometrial Oral Skin Melanoma Sow 10,500 7,925 6,900 46,000 67% 83% 29,600 53% 32,000 84% Intercourse at an early age; multiple set partners; smoking tarty menarche: ate menopause: obesity Smoking; eicessive use of alcohol Sunburn; fair complexion; exposure to coal tar, pitch, creosote, arsenic, radium R&S147552 K'J TlMi.. Al'Hll 2b, 19^-3