Document jkXrvDmZ8GE09r9j26BKLO7Z

VINYL CHLORIDE TOXICOLOGY Vinyl chloride despite its reported synthesis in 1835 did not become an article of commerce until 1928 when Union Carbide Corporation started research and pilot scale manufacture in 1928. This work was followed by commercial manufacture of vinyl chloride polymers in the United States by Union Carbide Corporation and in Germany during 1933. From this early start, the VC-PVC industry has grown to its present day level as one of the largest of the plastics industries. The earliest study of the toxicity of vinyl chloride was that reported by F. A. Patty. 51/ He found that human exposure to vinyl chloride at 2.5% for 3 minutes produced dizziness and disorientation and that guinea pigs exposed for eight hours at 0.5% showed no effect. Guinea pigs exposed to 2.5% for eight hours died. Patty also cited work by Schaumann 63/ that noted no hepatic or renal lesions occurred in mice or rats exposed at 0.5% for four hours daily over five to eight days. The apparent low toxicity of vinyl chloride as compared to chloroform, a widely used anes thetic at that time,led to its consideration as an anesthetic by Lehman and Flury 31/ after Peoples and Leak 53/ had confirmed its apparent low toxicity. Von Oettingen in 1933 cautioned against its use as an anesthetic. 88/ Later studies by Oster and Carr in 1947-1949 showed vinyl chloride used as an anesthetic caused UCC 070636 severe cardiac arrhythma. 4 8/ As late as 1955, vinyl chloride was still under consideration as an anesthetic. Von Oettingen cautioned as regards to its effect on the circulatory system. 87/ Many researchers cite the report of Tribukh in 1949 74/ that 73 workers in a PVC compounding and calendering plant showed hepatitis, hypertension, anemia, gastritis and skin lesions as evidence of the highly toxic nature of vinyl chloride retained in the PVC. The compounding was done at temperatures of 160C. using diphenylene*and chlorinated naphthalene as well as various pigments and stabilizers. Chlorinated naphthalene is well known as a severe liver toxicant and such symptoms have been observed in others exposed to such materials. Between 1953 and 1959, other problems related to additives were noted but there was no reported liver disease. The availability of better plasticizers which were less toxic no doubt contributed to the lack of further problems. 30/ The American Congress of Governmental Industrial Hygienists set the threshold limit value of vinyl chloride at 500 ppm for an eight-hour exposure based on human experience and animal data. This was believed to be a safe level for worker exposure. 70/ Mastromatteo in 1960, following the accidental death of two vinyl chloride workers, exposed rats, mice and guinea pigs to 10%, 20% and 30% vinyl chloride for 30 minutes. 37/ At the higher concentrations, the animals showed narcosis and respiratory failure. All animals showed lung, hepatic and renal congestion. Prodan reported LDjq of mice, rats, guinea pigs and rabbits based on two-hour exposure. 57/, 58/ The vinyl chloride concen tration varied from 12% for mice and 24% for rabbits. Surviving animals rapidly regained their normal appearance on cessation of exposure. A 90-day guinea pig exposure at 10% vinyl chloride resulted in liver and kidney lesions and lung fibrosis. Torkleson, et al, in 1961, initiated the first studies of vinyl chloride chronic toxicity. They reported micropathological changes in rats after 45 months at the then acceptable 500 ppm exposure level. Their minimum level was 100 ppm where rat livers showed only a slight increase in weight. No effect was noted in * Diphenylene is not a known material and may be an erroneous reference to chlorinated diphenyl which was used as a plasticizer and was also a liver toxin. 30/ UCC 070637 the other species (rabbits, dogs and guinea pigs) at this level. The researchers suggested a maximum worker exposure of 100 ppm with an eight-hour TWA of 50 ppm. 73/ Lester, et al, in 1962 reported that repeated exposure of rats to 2% and 5% vinyl chloride concentrations cause no signifi cant problems. They noted liver changes but decided they were not significant. Lester recommended a 500 ppm Threshold Limit Value. 32/ The ACGIH chose to give more weight to Lester's work than to Torkleson's and cut the recommended vinyl chloride TLV from an eight-hour TWA to a 500 ppm ceiling value. 70/ This value was subsequently written into the Occupational Safety and Health Act of 1970 as a Standard. Suciu, et al, in 1963 have been widely cited as sounding the alarm for vinyl chloride chronic toxicity but they reported on a cohort of vinyl chloride workers exposed for one year at a reported average concentration of 900 ppm. 64/ Based on prior knowledge, the worker dizziness and other symptoms were not unexpected. A later report in 1967 indicated that the acute exposure symptoms reported earlier were disappearing in an estimated exposure environ ment of 38 ppm. The year 1966 marked the observed onset of acroosteolysis and Reynaudfs syndrome. Cordier, et al, reported skin lesions and acroosteolysis in reactor cleaners. 82/ B. F. Goodrich's Dr. R. H. Wilson reported his observations to the Manufacturing Chemists Association. 94/ He had noted evidence of acroosteolysis since 1962. The Manufacturing Chemists Association in a meeting at Cleveland, late in 1966, reviewed the apparently new occupational disease with VC-PVC industry representatives. These industry representatives agreed to cooperatively sponsor an investigation of the purported disease and the University of Michigan Institute of Industrial Health was employed to conduct an epidemiological study. 82/ After a wide-ranging investigation, the University of , Michigan reported to MCA in 1969 that identification of the causative agent or agents was not conclusive; however, it would seem in order to reduce the severity of VC exposure by reactor cleaners and per- >w sonnel in the reactor area. The value of 50 ppm recommended by UCC 070638 Torkleson, et al, was endorsed. They also recommended that efforts to produce the disease in laboratory animals be supported by indus try. Dr. P. L. Viola, an industrial physician, 86/, 85/ was employed by Solvay, et cie, to study the acroosteolysis problem. In 1970 he reported that he had exposed 25 rats to 30,000 ppm vinyl chloride for twelve months. Thirteen died from cardio respiratory complications and two from abdominal hemorrhages. He noted lesions of the bone and connective tissue similar to acroosteolysis. 85/ He also noted degenerative processes of the parenthyma in the brain, liver and kidneys. Later that year at the Tenth International Cancer Congress in Houston, Texas, he reported that 26 rats exposed to 30,000 ppm vinyl chloride developed skin tumors (65%) and that 26% of those affected developed respiratory tract tumors. 83/, 84/ The epidermoid tumors were located in the vicinity of the ears. He stressed that the results applied only to rats and no implications to human pathology can be extrapolated. Later that year in an apparently unpublished paper, he noted that a maximum allowable concentration of 500 ppm for worker exposure gave an adequate margin of safety. 86/ The Manufacturing Chemists Association invited Dr. Viola to the United States to discuss his studies in greater detail. On May 5 and 6 of 1971, he reviewed his work in detail and referred to other research work underway in general terms. He claimed to have seen tumors in rats exposed to 5,000 ppm but reaffirmed his belief that 500 ppm TLV provided an adequate margin of employee safety from tumor induction. In November 1971 the Manufacturing Chemists Association convened a meeting of VC-PVC industry representatives to discuss the apparent vinyl chloride problem revealed by Dr. Viola. Dr. Le Fevre of Solvay, et cie, discussed European observations and stated generally that further European vinyl chloride toxicity studies were underway. Dr. Viola's work was discussed and the appearance of tumors in rats exposed to 5,000 ppm vinyl chloride confirmed. 91/ The group formed an Ad Hoc Committee under UCC 070639 R. N. Wheeler, chairman, to plan a cooperative research program. The MCA Committee proposed a program involving a three level three species chronic inhalation toxicity study, a study of vinyl chloride metabolism and an industry-wide epidemiological study of mortality at a cost of $350,000. Kramer and Mutchler in 1972 reported on a cohort of Dow employees exposed to vinyl chloride. 27/ They reported that life time exposure to 300 ppm vinyl chloride may result in slight changes in physiological and clinical parameters. The possibility of impair ment of liver function must be considered. The ACGXH as a result of the Kramer and Mutchler's report lowered its recommended TLV for workers to 200 ppm 8-hour TWA. 70/ Sponsorship of the Manufacturing Chemists Association study did not meet the financial objective of $350,000 so the decision was made to do the long-term inhalation study and postpone the other studies pending collection' of additional money. An MCA representative was sent to Europe to determine the nature of their program. He returned without any new information. During 1973 MCArhaving collected sufficient sponsorship, con tracted for the long-term inhalation toxicity, the metabolism and the epidemiological studies. The inhalation study was late in getting started due to relocation of the contractor and his failure to provide proper facilities. An MCA group composed of corporation executives established liaison with the European consortium sponsoring vinyl chloride research under Dr.- C. Maltoni. Informal reports on Dr. Maltoni's work revealed that the rats under test had shown tumors at the 250 ppm exposure level. These results and the substance of the planned research were discussed with Dr. M. Key and Associates at NIOSH in mid-summer. `1 On January 23, 1974, B. F. Goodrich Company reported that five Louisville, Kentucky PVC plant employees had died of angio- t sarcoma, a rare form of cancer. The preliminary reports on the European research confirmed that this cancer may be related to vinyl chloride exposure. 35/ UCC 070640 A preliminary report from Dr* C. Maltoni stated that rats exposed to long-term inhalation of vinyl chloride showed zymbal gland carcinomas, nephroblastomas, angiosarcomas, angiomas, hepatomas, brain neuroblastomas and skin carcinomas. Mice developed angiosarcomas, angiomas,lung adenomas, mammary carcinomas and skin tumors. Hamsters developed angiosarcomas, skin tumors and lymphomas. Common to all species were angiosarcomas. Nephroblastomas were common to rats and mice but are not known to appear in humans. Angiomas were also common to rats and mice. 64/ The appearance of angiosarcomas in the mice used in the MCA test confirmed Maltoni's work. 64/ Juhe, Lange, et al, reporting in late 1973 on the vinyl chloride disease notes that at exposures of 60 to 1,000 ppm, they had seen fibrotic livers via laparotomy and seen possible lung fibrosis in employees of PVC plants. 26/ i.i--r- Skin absorption by vinyl chloride was studied by Hefner, alj of Dow Chemical. A Rhesus monkey exposed to 7,000 ppm vinyl s via skin for two hours was estimated to be equal to the inhalation by a man of 0.185 ppm for eight hours, 95/ With the connection between animal biossay and human disease via angiosarcoma concern then shifted to the nature and extent of vinyl chloride caused neoplasms in the work force and in the people living in the area of VC-PVC facilities. Waxweiler, et al, in 1976 reported on a survey of four PVC plants whose workers were exposed to high levels of vinyl chloride. Based on 136 deaths, they reported excesses of brain, central nervous system, respiratory, liver and lymphatic neoplasms. 90/ " ~~ Gamble, et al, in 1976 reported that vinyl chloride workers did not show chronic respiratory effects related to their exposure but smoking caused acute reductions. 19/ A study of Union Carbide Corporation workers at the South Charleston, West Virginia Plant showed excesses of angiosarcomas. All malignancies had a standardized mortality ratio of 87.7 compared to 111 for all other industry PVC-VC workers. Only leukemia and lymphomas were in excess but only eight cases were reported. This 'study UCC 070641 covered 1,314 workers and 211 deaths. Forty-nine percent of the study group had twenty years or more employment in vinyl chloride work. 16/ Fox and Collier in 1977 reported that an epidemiological study of vinyl chloride workers in Great Britain showed excess liver cancers but no evidence that vinyl chloride was a general carcinogen. The study covered 7,714 workers and 409 deaths. 18/ The Manufacturing Chemists Association industry-wide VC-PVC worker study on 10,173 workers and 669 deaths showed excessive standardized mortality ratios for brain tumors, miscellaneous cancers and leukemia but the numbers of cases were small. 72/, 96/ The conclusion of this study was that there maybe some support for the hypothesis that vinyl chloride is a general carcinogen. Con sidering that the previously noted Union Carbide Corporation study made up part of this study .and the Union Carbide Corporation workers made up a major portion of those exposed for a long period, the conclusions from the comparison of the two studies are not consistent. The PVC fabricating industry was the subject of two studies. One by Organization Resources Counselors in the United States reported no angiosarcomas in 4,592 deaths. 14/, 45/, 46/ Proportional mortality ratios showed excess deaths in digestive, respiratory and all other neoplasms as well as deaths from circulatory disease. There was a significant depression in deaths from all other causes indicating a lack of complete data. Dr. G. M. Paddle in a letter to R. N. Wheeler observed that the apparent excesses in PMR's *-l were a common feature of industrial employee studies. 50/ Baxter and Fox in 1976 reported that there was no excess risk of lung, brain or liver cancer in PVC fabricators in Great Britain* In the period 1963-1973, they found only one case of angio sarcoma relatable to VCM out of an average of four cases per year for the period. They noted that most of the four per year were mis diagnosed and there were actually only fourteen cases of AS *-2 in ten years. 9/, 10/ Brady, et al, in 1977 reported on twenty-six New York State angiosarcoma cases. Three had had contact with vinyl chloride in *-l Proportional Mortality Ratio *-2 Angiosarcoma UCC 070642 their work and five lived within 4,500 feet of a VCM or PVC plant. They concluded that since the rate of AS cases in Now York was 0.25 per million of population versus the national average rate of 0.14, there must be'other causes of AS than Thorotrast, arsenicals and vinyl chloride. 97/ MacMahon 34/ and Downs, 15/ et al, in critcal reviews of the reports on mutagenesis, fetal anomalies or fetal death' reported while there was some evidence of VC caused chromosome aberrations there is no evidence of VC caused fetal wastage or birth defects. 89/, 24/ A tabulation of VC-PVC related angiosarcoma cases is as follows: Year 1961 1964 1968 Company and Location -Goodyear, Niagara Falls, .New York -B. F. Goodrich, Louisville, Kentucky --Union Carbide, South Charleston, West Virginia -Goodyear, Niagara Falls, New York 1969 `-B. F. Goodrich, Louisville, Kentucky -Firestone Plastics, Pottstown,. Pennsylvania . 1970 1971 -B. F. Goodrich, Louisville, Kentucky 'Goodyear, Niagara Falls, New York -B. F. Goodrich, Louisville, Kentucky 1973 - B. E. Goodrich, Louisville, Kentucky B. F. Goodrich, Louisville, Kentucky 1974 "Union Carbide, South Charleston, West Virginia 1975 -*B. F. Goodrich, Louisville, Kentucky <*B. B. F. Goodrich, Louisville, Kentucky F. Goodrich, Louisville, Kentucky 1976 -Union Carbide, South Charleston, West Virginia 'B. F. Goodrich, Louisville, Kentucky 1977 -Great American Plastics, Massachusetts Union Carbide, South Charleston, West Virginia " Union Carbide, South Charleston, West Virginia From this tabulation of angiosarcoma cases, it is evident that it could not have been concluded prior to 1974 that there was UCC 070643 an excess of angiosarcoma cases in the industry. Approximately 2C cases of angiosarcoma are diagnosed each year in the United States from all causes 28/. From this survey of vinyl chloride toxicology, the follow ing conclusions may be drawn: 1. Based on the information available to it the VC-PVC industry and Union Carbide Corporation acted in a responsi ble manner. In retrospect, speedier action might have expedited the report of the carcinogenic properties of vinyl chloride by no more than one year. 2. Vinyl chloride exposure has been connected with angio sarcoma in humans. No other type of neoplasm has been identified as specifically caused by human vinyl chloride exposure, 3. Vinyl chloride exposure has been related to acroosteolysis in humans. R. N. Wheeler April 10, 197S i UCC 070644 LITERATURE CITED Adams, W.G.F. and Purchase, "Is PVC Dust a Hazard?", Unpublished Communication, Imperial Chemical Industries, Ltd., Welwyn Garden City, Herfordshire, England, July 23, 1975. Baretta, E. D., et al,: "Monitoring Exposures to Vinyl Chloride Vapor - Breath Analysis and Continuous Air Sampling" , American Industrial Hygiene Association Journal, p. 537, Vol. 30, 1969. Baxter, P. J., et al,: "Angiosarcoma of the Liver in Great Britian 1963-1973:, British Medical Journal, pp. 919-921, Vol. 2, 1977. Baxter, P. J. and Fox, A. J.: "Angiosarcoma of the Liver in P.V.C. Fabricators", The Lancet, January 31, 1976. Verband Kunststofferzeugende Industrie E.V. (VKE) "VC/PVC: Beispiel einer Problemlosung", Frankfurt/Main, 1975. Carr, J., et al,: "Chemical Constitution of Hydrocarbons and Cardiac Automaticity", Journal of Pharmacology Exptl, Ther. 97, 1, 1949. UCC 070645 Chiazze, L. , Jr., Nichols, W. E., and Wong, Otto: "Mortality Among Employees of PVC Fabricators", Journal of Occupational Medicine, Vol. 10, No. 9, September 1977. Downs, T. D., et al,: "Vinyl Chloride, Birth Defects and Fetal Wastage, A Critical Review", The Society of the Plastics Industry, September 16, 1977. Equitable Environmental Health, Inc.,: "Epidemiologic Study of Vinyl Chloride Workers Employed by Union Carbide Corporation, South Charleston Plant", 2180 Milvia Street, Berkeley, California 94704, December 1976. Falk, Henry, et al,: "A Cross-Sectional Epidemiologic Survey of Vinyl Chloride Workers", United States Department of Health, Education and Welfare, National Institute for Occupational Safety and Health, Cincinnati, Ohio, April 1977. Fox, A. J., et al,: "Mortality Experience of Workers Exposed to Vinyl Chloride Monomer in the Manufacture of Polyvinyl Chloride in Great Britain", British Journal of Industrial Medicine, pp. 1-10, Vol. 34, 1977. i Gamble, J., Shuguey L., McMichael and Waxweiler: "Effect of Occupational and Non-Occupational Factors on the Respiratory System of Vinyl Chloride and Other Workers", Journal of Occupational Medicine, Vol. 18, No. 10, October 1976. Gehring, P. J., et al,: "Resolution of Dose-Response Toxicity Data for Chemicals Requiring Metabolic Activation: Example Vinyl Chloride", Dow Chemical U.S.A., Midland, Michigan 48640, July 12, 1977. Health and Safety Executive: "Vinyl Chloride, Code of Practice for Health Precautions", London, 1975. UCC 070646 24. Infante, P. F., et al,: "Carcinogenic, Mutagenic and Teratogenic Risks Associated with Vinyl Chloride", Mutation Research, pp. 131-142, Vol. 41, May 13, 1976. 26. 27. 28. 29. 30. 31. 32. Juhe, S., Lange, G., Stein, G., and Veltman, G.: "On the So-Called Vinyl Chloride Disease", University Skin Clinic of Bonn, Deutsche Medizinische Wochenschrife, 98 (43), pp. 2034-2037, 1973. Kramer, C. G., et al,: "The Correlation of Clinical and Environmental Measurements for Workers Exposed to Vinyl Chloride", American Industrial Hygiene Journal, January 1972. Kuzmach, A. and McGaughy, R.,: "Quantitative Risk Assess ment for Community Exposure to Vinyl Chloride", United States Environmental Protection Agency, 1975. Lee, C. C., Bhandari, J. C., et al,: "Carcinogenicity of Vinyl Chloride and Vinylidene Chloride", Journal of Toxicology and Environmental Health; Pharmacology & Toxicology, Midwest Research Institute, Kansas City, Missouri 64110 and Environ mental Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C. 27709,ABSTRACT, 32, 1977. LeFaux, R.: "Practical Toxicology of Plastics", Ileffe Books Ltd, London, pp. 142-144, pp. 37-371, 1968. Lehman, K. B. and Flury, F., Toxicology and Hygiene of Industrial Solvents, Williams and Wilkins Company, 1943. Lester, D., et al,: "Effects of Single and Repeated Exposures of Humans and Rats to Vinyl Chloride", American Industrial Hygiene Association Meeting, Washington, D.C., May 1962. 34. 1 MacMahon, Brian, M.D.: "Vinyl Chloride and Human Reproduction", The Society of the Plastics Industry, Vinyl Chloride - Polyvinyl Chloride Safety Group, August 15, 1977. UCC 070647 35. 36. 37. 38. 39. Manufacturing Chemists Association (MCA): "Vinyl Chloride Chronology", MCA-3846 - 1825 Connecticut Avenue, N.W., Washington, D.C. 20009, May 10, 1974. Maricq, Johnson, Whetstone & LeRoy: "Capillary Abnormalities in Polyvinyl Chloride Production Workers", JAMA, Vol. 236, No. 12, September 20, 1976. Mastromatteo, E., et al,: "Acute Inhalation Toxicity of Vinyl Chloride to Laboratory Animals", American Industrial Hygiene Association Journal, p. 394, Vol. 5, 1960. Bulletin Hygiene, 36:244. ' Mutchler, J. E., et al,: "Report on the Relation of Exposure to State of Health of Dow Chemical Workers", Gordon Conference, Tilton, New Hampshire, August 1968. National Institute for Occupational Safety and Health: "Recommended Standard for Occupational Exposure to Vinyl Chloride", United States Department of Health, Education and Welfare, 1974. < 45. 46. * Organization Resources Counselors, Inc.: "Report on a Mortality Study Covering Employees of PVC Fabricators", 1625 I Street, N.W., Washington, D.C. 20006, February 1976. Organization Resources Counselors, Inc.: "Report on a Case Control Study Covering White Female Employees of PVC Fabricators". May 1977. UCC 070648 Occupational Safety and Health Administration Emergency Temporary Standard for Exposure of Vinyl Chloride, United States Department of Labor, April 5, 1974. Oster, R. H., et al,: "Narcosis with Vinyl Chloride", Anesthesiology, Vol. 8, p. 359, 1947. Ott, M. G., Langner, R. R., and Holder, B. B.: "Vinyl Chloride Exposure in a Controlled Industrial Environment", Arch Environ Health. Vol. 30, July 1975. Paddle, G. M.: "Report on a Mortality Study Covering Employees of PVC Fabricators". (Personal Letter to Mr. R. N. Wheeler, Jr. - letter written to: Dr. j. Stafford, Health and Environment Dept., ICI Plastics Division, Welwyn), July 13, 1977. Patty, F. A., et al,: "Acute Response of Guinea Pigs to Vapors of New Commercial Organic Compounds", Public Health Report, 45, 1963. Patty, F. A.: "Industrial Hygiene and Toxicology". Vol. II, BUS-1307, John Wiley and Sons, New York, New York, 1962. Peoples, A. S. and Leake, C. D.: Journal of Pharmacology, Vol. 48, p. 284, 1933. Picciano, Flake, Gay and Kilian: "Vinyl Chloride Cytogenetics", Journal of Occupational Medicine. Vol. 19, No. 8, August 1977. Prodan, L., et al,: Intoxicatia conica cu clorura de vinil, Ses. St. 1 MF Cley Romania, 1969. Prodan, L. and Suciu I, et al,: "Experimental Acute Toxicity of Vinyl Chloride". Toxicity of Vinyl Chloride - Polyvinyl Chloride, New York Academv of Sciences, Vol. 246, pp. 154-158, T97F:-- UCC 070649 59. Richardson, H. L.: "Angiosarcoma of the Human Liver",' U.S. Environmental Protection Agency, April 17, 1974, 63. 64. 65. 66. Schaumann, O., MED 0. CHEMIE, Vol. 2, p. 139 (cited by Dr. P. L. Viola), 1931. Selikoff, I. J. and Hammond, E. C.: "Toxicity of Vinyl Chloride - Polyvinyl Chloride", New York Academy of Sciences, Vol. 246, 1975. (a) Suciu, et al,: "Chemical Manifestations in Vinyl Chloride Poisoning", pp. 53-69. (b) Maltoni, et al,:"Carcinogenicity Bioassays of Vinyl Chloride Current Results",pp. 195-218. (c) Volkheimer:"Hematogeneous Dissemination Ingested Poly vinyl Chloride Particles",p. 164. (d) Keplinger, et alf:"Interim Results of Exposure of Rats, Hamsters and Mice to Vinyl Chloride",pp. 219-230. Smith, P. M., Williams, D.M.J. and Evan, D.M.D,: "Hepatic Angioscarcoma In a Vinyl Chloride Worker", Bulletin of the New York Academy of Medicine, May 1976. Smyth, H. F., Jr.: "Improved Communications - Hygiene Standards for Daily Inhalation", American Industrial Hygiene Association Journal, p. 129, 17, 195FI 68. Stafford, John: Letter to Dr. T. Torkelson, Dow Chemical, containing a tabulation of worldwide cases of angiosarcoma, July 29, 1977. UCC 070650 69. 70. Stafford, John: "Vinyl Chloride Disease" or "Vinyl Chloride Directive No. 2", Imperial Chemical Industries Limited (ICI) of London - covering regulations on vinyl chloride for Germany, The Society of the Plastics Industry, Inc., December 1977. 8, Torkelson, T. R.: "Statement of the Manufacturing Chemists Association Before the Subcommittee on the Environment of the Senate Committee on Commerce on Vinyl Chloride", MCA, August 21, 1974. 72. 73. 74. 75. 76. 77. 78. 79. Tabershaw/Cooper Associates, Inc.: "Epidemiological Study of Vinyl Chloride Workers", 2180 Mllvia St., Berkeley, California 94704, May 3, 1974. Torkelson, T. R.,'et al,: "The Toxicity of Vinyl Chloride as Determined by Repeated Exposure of Laboratory Animals", American Industrial Hygiene Association Journal, p. 354, 22, Number 5, 1961. Tribukh, S. L., et al, Giqenia Sanit., 10:38, 1949, quoted by Marsteller, et al,: "Splenomegalic Liver Disease", Toxicity of Vinyl Chloride .- Polyvinyl Chloride, New York Academy of Sciences, Vol". 246, 1975. Union Carbide Corporation: "Statement of Carl U. Dernehl, M.D., Associate Medical Director, prepared for Presentation at the Department of Labor Hearings on Vinyl Chloride Occupational Exposure Standard, June 25, 1974." Union Carbide Corporation's Testimony, OSHA Public Hearing, Docket OSH-36, June 25, 1974. Occupational Safety and Health Administration, "Standard for Exposure to Vinyl Chloride".(29 CFR 1910.1017) U.S. Department of Labor, Federal Register 35), pp. 35890-35898,pp. 41848,1974. Occupational Safety and Health Administration, "Vinyl Chloride, Proposed Standard", U.S. Department of Labor Federal Register 39, pp. 16896-16900, 1974. United States Environmental Protection Agency: "Scientific and Technical Assessment Report on Vinyl Chloride and Polyvinyl Chloride" , EPK-600/6-75-004, 1975. UCC 070651 80. United States Environmental Protection Agency: "Standard Support and Environmental Impact Statement, Emission Standard for Vinyl Chloride", Vol. II, 1976. 81. 82. United States Environmental Protection Agency: "Standard Support and Environmental Impact Statement, Emission Standard for vinyl Chloride", 1975. The University of Michigan: "Epidemiological Investigation of the Polyvinyl Chloride Industry in Reference to Occupational Acroosteolysis", The Institute of Industrial Health, February 1969. 83. Viola, P. L.: "Cancerogenic Effect of Vinyl Chloride", Regina Elena Institute for Cancer Research, University of Perugia, Tenth International Cancer Congress, Houston, Texas, May 22, 1970. 84. . Viola, P. L.: "Oncogenic Response of Rat Skin, Lungs and Bones to Vinyl Chloride", Cancer Research, pp. 516-522, Vol. 31, 1971. 85. Viola, P. L.: "Pathology of Vinyl Chloride", Medicina del Lavoro, Vol. 61, pp. 174-179, March 1970. 86. Viola, P. L.: "The Vinyl Chloride Disease", Unpublished Communication, Summer, 1970. 87. Von Oettingen, W. F.: "The Halogenated Hydrocarbons, Toxicity and Potential Dangers", U.S. Public Health Service Publication Mo. 414, Government Printing Office, Washington, D.C., 1955. 88. Von Oettingen, W. F., U.S. Public Health Service Publication ,, No. 411, U.S. Government Printing Office, Washington, D.C., 1933. 89. Wagoner, Infante and Brown: "Genetic Effects Associated with Industrial Chemicals", Industrywide Studies Branch, Div. of Surveillance, Hazard Evaluation and Field Studies, National Institute for Occupational Safety and Health, Cincinnati, Ohio. 1976 90. Waxweiler, et al,: "A Cross-Sectional Epidemiologic Survey of Vinyl Chloride Workers", Department of Health, Education and Welfare, Cincinnati, Ohio, April 1977. UCC 070652 91. Wheeler, R. N. , Jr.: "Manufacturing Chemists Association Occupational Health Committee - Vinyl Chloride Conference", Union Carbide Corporation, November 23, 1971. 94. 95. 96. 97^ Wilson, R. H. , et al," "Occupational Acroosteolysis", Journal of American Medical Association, Vol. 21, No. 8, 1967. Hefner, R., Watanabe, P., G^hring, P.: "Percutaneous Absorption of Vinyl Chloride (VCM) Gas in the Rhesus Monkey", Dow Chemical U.S.A., Midland, Michigan, 1974. Equitable Environmental Health, Inc.: "Epidemiological Study of Vinyl Chloride Workers - Final Report",2020 Milvia St., Berkeley, California 94704, August 1977. Brady, J., et al,: "Angiosarcoma of the Liver: An Epidem iologic Survey". J National Cancer Inst., Vol. 59, No. 5, November 1977. Deleted items are those unrelated to vinyl chloride hazards. RNW 6/27/34 4 RNWJ r./ws April 10, 1978 S UCC 070653 LITERATURE - SUPPLEMENTAL LISTING This listing, along with the preceding lists, is a "best efforts" compilation of available material on health effects of vinyl chloride available at Union Carbide Corporation, South Charleston, West Virginia. RNWJr. /ws April 11, 1978 R. N. Wheeler, Jr. UCC 070654 SX. 52. 53. 54. 55. 56. 57. 58. 59. S10. Ott, Langer and Holder: "Vinyl Chloride Exposure in a Controlled Industrial Environment", Archives Environmental Health, pp. 333-339, Vol. 30, July 1975. Heath, C. W., et al,: "Hemangiosarcoma of the Liver Connecticut", U.S. Public Health Service, CDC, Atlanta, Ga., 1974. Edmonds, L. D., et al,: "Congenital Central Nervous System Malformation - Kanawha County, W. Va.", U.S. Public Health Service, CDC, Atlanta, Ga., 1976. Theriault, G. P., et al,: "Birth Defects in a Community Located Near a Vinyl Chloride Plant", Dept, of Social and Preventive Medicine, Laval University, Quebec, 1977. Edmonds, L. D., et al,: "Congenital Malformation and Vinyl Chloride", The Lancet, November 1975* Duck, B. W., et al,: "Mortality Study of Workers in a Poly vinyl Chloride Production Plant", The Lancet, December 1975. Public Health Service: "Angiosarcoma of the Liver-wisconsin", Morbidity and Mortality, U.S. HEW 25, February 28, 1976. Infante, P. F., et al,: Genetic Risks of Vinyl Chloride"' NIOSH, U.S. HEW, Cincinnati, Ohio. Infante, P. F., et al,: "Oncogenic and Mutagenic Risks in Communities with Polyvinyl Chloride Production Facilities", New York Academy of Sciences, New York, 1975. State of California: "Effects of Airborne Vinyl Chloride", Air Resources Board, Sacramento, California, 1977. 512. 513. United States Coast Guard: "Vinyl Chloride Carriage Require- ments". Federal Register. Vol. 40, pp. 17024-17026, 1975. Picciano, D. J., et al,: "Vinyl Chloride Cytogenetics", Journal of Occupational Medicine, 1, pp. 527-530, 1977. S15. Sax, N. I., Dangerous Properties of Industrial Materials. Van Nostrand/Rernhold Company, 1975. UCC 070655 516. 517. 518. 519. 520. 521. Edmonds, Larry: "Birth Defects and Vinyl Chloride", Proceedings Conference on Women and the Workplace, Society for Occupational and Environmental Health, 1976. Environmental Protection Agency: "Preliminary Assessment of the Environmental Problems Associated with Vinyl Chloride and Polyvinyl Chloride", Washington, D.C., 1974. Environmental Protection Agency: "Environmental Aspects of Vinyl/Polyvinyl Chloride", Research Triangle Park, N.C., 1974. Japanese PVC Association: "Vinyl Chloride Monomer Probl ro in Japan". Copied by MCA, Washington, D.C., 1974. Wheeler, R. N., Jr.: "British and German Regulations Regarding Vinyl Chloride", Union Carbide Corporation, South Charleston, W. Va., 1975. German Society of Plastics Industry: "VC/PVC Measures for Health Protection", Frankfurt/Main, 1974. 523. 524. 525. Department of Employment: "Vinyl Chloride Code of Practice", London, 1974. Gibson, D. G.: "Vinyl Chloride Occupational Health Standard", Alberta, Canada, 1975. German Professional Cooperative Society of the Chemical Industry: "Informatory Discussion Concerning Current Problems of Working Safety and Medicine in the Processing of Vinyl Chloride", Frankfurt/Main, 1975 527. 528. 529. , Hathway, D. E. : "Comparative Mammalian Metabolish of Vinyl and Vinylidene Chloride in Relation to Oncogenic Potential", Environmental Health Perspectives, Vol. 21, 1977. Drabble, R.: "VCM Equipment Investigation", Imperial Chemical Industries, Welwyn Garden City, 1974. Industrial Biotest Laboratories, Inc.: "23-Month Status Summary to Manufacturing Chemists Association, Chronic Vapor Inhalation Toxicity Study with Vinyl Chloride in Albino Rats, Albino Mice and Golden Hamsters", Northbrook, Illinois, 1975. UCC 070656 530. 531. 532. 533. 534. Wheeler, R. N., Jr.: "Notes on Vinyl Chloride Medical ' Surveillance Workshop, University of Louisville", Union Carbide Corporation, N.Y., N.Y., 1977. Thiess, A. M., et al,: "Retrospective Survey of the Alleged Diseases Associated with Vinyl Chloride in the Federal Republic of Germany", Journal of Occupational Medicine, 11, pp. 430-432, 1975. Stockinger, H.E.: "Sanity in Research and Evaluation of Environmental Health", Science, Vol. 174, pp. 662-669, 1971. Frenes-Cravioto, F., et al,: "Chromosome Aberrations in Workers Exposed to Vinyl Chloride", The Lancet, p. 459, 1975. ----------------------- Block, J. B.: "Angiosarcoma of the Liver Following Vinyl Chloride Exposure", JAMA, Vol. 229, pp. 53-54, 1974. 536. 537. 538. 539. 540. 541. 542. Eckardt, R. E. and Hinden, R.: "The Health Hazards of Plastics", Journal of Occupational Medicine, Vol. 15, pp. 808-819, 1973. Lane, K. S.: "Meeting with Professor Maltoni, International Hotel, New York, June 5, 1974", Union Carbide Corporation, N.Y., N.Y., 1974. Maltoni, C., et al,: "Carcinogenicity Bioassays of Vinyl Chloride", Environmental Research, Vol. 7, June 1974. Maltoni, C., et al,: "Le potinzralita' dei saggi spirimentali nella pred zone de reschi oncogeni ambientale. esempio" il cloruro di vinile", Accademia Nazionale Dei Lincei, Rome, 1974. Maltoni, C., et al,: "Insorgenza di angiosarcomi in ratti in segruto a Sanmincstrazione per via orale di cloruro di vinile", Ospedali di bologna, 1975. Maltoni, C.: "Occupational Carcinogenesis", Proceedings of the Second International Symposium on Cancer Detection and Prevention, April 1973. Maltoni, C.: "Letter to John Stender, U.S. Department of Labor", August 13, 1974. UCC 070657 543. Maltoni, C., et al,: "Preliminary Report on Carcinogenicity Biossays of Vinyl Chloride", Isituto di Oncologia *F Addarii" and Centro Tumori, Bologna, Italy, November 1974. 544. Maltoni, C., et al,: "la cancerogenesi ambientale e profes- sionale nuove prospettive alia luce della cancerogenesi da cloruro di vinile", Istituto di Oncologia e Centro Tumosi, Bologna, Italy, 1974. 545. Reynolds, E. S., et al,: "Hepatotoxicity of vinyl Chloride and Related Chemicals", Federation of American Societies for Experimental Biology, Atlantic City, N.J., 1975 546. Reynolds, E. S., et al,: "Modulation of Halothane and Vinyl Chloride Induced Acute Injury to Liver Endoplasmic Reticulum", National Institute of Health Grant, Peter Bent Brigham Hospital, Boston, Mass., 1975. 547. Reynolds, E. S., et al,: "Acute Liver Injury by Vinyl Chloride, Involvement of Endoplasmic Reticulum in Phenobarbital Pre treated Rats", National Institute of Health Grant,Peter Bent Brigham Hospital, Boston, Mass., 1975. 548. National Institute for Occupational Safety and Health", Recommended Occupational Health Standard for the Manufacture of Synthetic Polymer from Vinyl Chloride", U.S. Dept, of Health Education and Welfare, March 1974. 549. Waggoner, J. K., et al,: "Genetic Effects Associated with Industrial Chemicals", National Institute for Occupational Safety and Health, Department of HEW, 1976. 550. Bartsch, H., et al,: "Mutagenicity of Vinyl Chloride, Chloroethylenoxide, Chloroacetaldehyde and chloroethanol", Biochemical and Biophysical Research Communications, Vol. 63, p. 363, 1975. 551. Thomas, L. B., et al,: "Vinyl Chloride Induced Liver Disease", The New England Journal of Medicine, Vol. 292, pp. 17-22, 1975: 552. National Institute for Occupational Safety and Health, Industrial Hygiene Survey of the Union Carbide Corporation Polyvinyl Chloride Operations, South Charleston, W. Va., NIOSH, Cincinnati, Ohio, 1975. 553. , Bendix Corporation: "Environmental/Industrial Hygiene Surveys of Vinyl Chloride Monomer Manufacturing Operations and Operations Where Polyvinyl Chloride and Copolymers of Poly vinyl Chloride are Processed", NIOSH, 1975. UCC 070658 554. 555. 556. 557. 558. 559. 560. Grivas, A. S.: "Letter and attachments to R. W. Holland, M.D., Union Carbide Corporation, South Charleston, W. Va.", ProtocolEvaluation of Medical Screening for the Detection of Liv r Disease Among Vinyl Chloride Workers", U.S. Public Health Service, 1974. Spirtas, R., et al,: "The Association of Vinyl Chloride Exposures with Morbidity Symptoms", American Industrial Hygien Conference, Minneapolis, Minn., 1975. Eisenhour, M. E.: "OSHA Officials Visit to Texas City Plant", Union Carbide Corporation, Texas City, Texas, 1974. Occupational Safety and Health Administration, "Industrial Hygiene Survey Report on Vinyl Chloride and Polyvinyl Chloride Manufacturing Facilities", Office of Standards Development, OSHA, U.S. Dept, of Labor, 1974. Occupational Safety and Health Administration: "Final Environ mental Impact Statement, Proposed Regulation Vinyl Chloride", OSHA, U.S. Dept of Labor, 1974. Stender, J. H.: "OSHA Program Directive #200-35 (Vinyl Chloride)", OSHA, U.S. Dept, of Labor, 1975. Cox, R. A., et al,: "The Photochemical Reactivity of Vinyl Chloride", Environmental and Medical Sciences Division AERE, Harwell, 1974. S62. Union Carbide Corporation: "Vinyl Chloride", Reaction and Hazardous Chemicals Manual",Union Carbide Corporation, N.Y., N.Y., 1972. i UCC 070659 568. 569. 570. 571. 572. 573. 574. 575. 576. 577. 578. Watanabe, P.G., et al,: "Summary of the Studies Conducted on Pharmcokinetics/Metabolism of Vinyl Chloride in Rats", Manufacturing Chemists Association, Washington, D.C., 1977. Watanabe, P. G., et al,: "Hepatic Macro-molecular Binding Following Exposure to Vinyl Chloride", Manufacturing Chemists Association, Washington, D.C., 1977. John, J. A., et al,: "The Effects of Maternally Inhaled Vinyl Chloride on Embryonal and Fetal Development in Mice, Rats and Rabbits", Manufacturing Chemists Association, Washington, D.C., 1976. Watanabe, P. G., et al,: "Fate of 14C - Vinyl Chloride After Single Oral Administration in Rats", Manufacturing Chemists Association, Washington, D.C., 1975. McGowan, G. R., et al,: "Vinyl Chloride Urinary Metabolites: Identification and Isolation", Manufacturing Chemists Association, Washington, D.C., 1975. Johnston, R. v., et al,: "Cytogenetic Studies of Bone Marrow Cells from Rats Exposed to .Vinyl Chloride", Dow Chemical, U.S.A., Freeport, Texas, 19'75. Dow Chemical, U.S.A.: "Continued Studies on the Pharmcokinetics/ Metabolism of Vinyl Chloride in Mammals", Manufacturing Chemists Association, Washington, D.C., 1975. Schwetz, B. A., et al,: "Results of a Vinyl Chloride Teratology'Study in Mice, Rats and Rabbits", Society of Toxicology, Williamsburg, Va. Meeting 1975. Gehring, P.J., et al,: "Preliminary Studies of the Fate of Inhaled Vinyl Chloride Monomer in Rats", New York Academy of Sciences, 1974. Hefner, R. E., et al,: "The Effects of Exposure of Rats to vinyl Chloride on the Sulfhydryl Levels of Liver", Dow Chemical, U.S.A., for Manufacturing Chemists Association, 1973. Wheeler, R. N., Jr.: "Seminar Workshop - Cancer Center, University of Louisville Notes", Union Carbide Corporation, N.Y., N.Y., April 6-7, 1976. UCC 070660 579. 580. Laumback, A. D., et al,: "Studies on the Mutagenicity of Vinyl Chloride Metabolites and Related Chemicals", Third International Symposium on Detection and Prevention of Cancer, N.Y., N.Y., 1976. University of Louisville Cancer Center: "Technical Proposal Research Techniques and Methods for Detection and Prevention of Carcinogenesis in Industrial Workers", October 31, 1975 (supported by Manufacturing Chemists Association.) S84. University of Louisville: "Initial Progress Report for the Manufacturing Chemists Association's (Research) Agreement with the University of Louisville, Louisville, Ky,, 1977, 586. 587. 588. 589. J 590. Green, T. and Hathaway, D.E.: "The Chemistry and Biogeneses of the S-Containing Metabolitis of vinyl Chloride in Rats", Chem.-Biol* Interactions, Vol. 17, pp. 137-150, 1977, Withey, J. R., et al,: "A Statistical Assessment of the Quantitative Uptake of Vinyl Chloride Monomer from Aqueous Solution", Journal of Toxicology and Environmental Health, Vol. 2, pp. 311-321, 1976. Fiechtner, J. J., et al,: "Angiosarcoma of the Liver in a Rural Population", JAMA, Vol. 236, pp, 1704-1706, 1976, Heckman, J.: "Letter to Mr, R. Ronk of FDA re PVC, 90-week Interim Report of Two-Year Oral Toxicity Study Conducted by CIVO-TNO", Keller and Heckman for S.P.I., Washington, D,C., 1976. Maltoni, c.: "Report on the Results of the Experiments BT 9, BT 15 and BT 17, Respectively, after 100 and 87 Weeks", Council of European Chemical Industry Federation, 1976. UCC 070661 S91 Feron, V. J., et al,: "Observations on the Oral Administration and Toxicity of Vinyl Chloride in Rats"/ Food-Cosmetic Toxicology, Vol. 13, pp. 633-638, Great Britain, 1975. 596. 597. 598. 599. Fraumeni, J. F., Persons at High Risk of Cancer, Academic Press, N.Y., 1975. Kraybill, h. F.: "From Mice....................to Men", Conference on Human Epidemiology and Animal Laboratory Correlations in Chemical Carcinogenesis, Mescalero, N.M., 1977. European Council of Chemical Manufacturers Federationsr Vinyl Chloride Toxicity and the Use of PVC for Packaging Foodstuffs", Brussels, 1976. Wilson, Richard: "Risk-Benefit Analysis for Toxic Chemicalst Vinyl Chloride", Harvard University, Cambridge, Mass., 1976. Deleted items do not deal with vinyl chloride hazards. RNW 6/27/84 i UCC 070662 LITERATURE - SECOND SUPPLEMENTAL LIST RNW 6/28/84 551. Conference to Reevaluate the Toxicity of Vinyl Chloride, Polyvinyl Chloride and Structural Analogs. Environmental Health Perspectives, Vol. 41, October 1981. 552. McMillin, C. R., et al. Potential Atmospheric Carcinogens Phase 1 Identification and Classifications US EPA, January 1980. : 553. The Physiological Effects .of Vinyl Chloride and Polyvinyl Chloride, Volumes I & 2, Daniel P. Boyd and Co.. Leesburg. Va., 1981. 554. Research Techniques and Methods for the Detection and Prevention ot Carcinogenesis in the Industrial Worker, Report for CMA, University of Louisville, Health Services Center, School of Medicine, 1982. 555. Hiatt/Watson/Winsten, Origins of Human Cancer, Books A, B and C, Cold Spring Harbor Laboratory, New York, 1977. 556. Veltman, G, et al. Clinical Manifestations and Course of Vinyl Chloride Disease, Annals New York Academy of Sciences, Volume 246, 1975. 557. Tribukh, S. L., et al. "Working Conditions and Measures for their Improvement in Production and Use of Vinyl Chloride Plastics", Gigiena i Sanct., (10):38-44, 1944. Translated by A. D. McCormick Co., Dunbar, W. Va. 558. Gauvain, S., "Vinyl Chloride: Introduction to the Problem" Proceedings Royal Medical Society, Vol. 69, 1976. 559. Monsori, R. R., et al. "Proportional Mortality Among Vinyl Chloride Workers", Environmental Health Perspectives, Vol. 11, pp. 75-77, 1975. 5510. Austin, S. G., et al. "A Cohort Mortality Study of Petro chemical Workers:, Journal of Occupational Medicine, Vol. 25, April 1983: ' 5511. Austin, S. G., et al. "A Case-Control Study of Chemical Exposures and Brain Tumors in Petrochemical Workers". Journal of Occupational Medicine, Vol. 25, No. 4, 1983. 5512. Feron, V. J., et al. "Lifespan Oral Toxicity Study of Vinyl Chloride in Rats", Food and Cosmetic Toxicology, Vol. 19, pp. 313-333, 1981: UCC 070663 5513. Thereault, G. P., et al. "Association Between Birth Defects and Exposure to Ambient Vinyl Chloride", US E.P.A., Research and Development, EPA-600/S 1-81-057, Sept. 1981. 5514. Ungvary, G., et al. "Study of the Teratogenic and Embryotoxic Effect of Vinyl Chloride in CFY Rats", National Institute of Occupational and Industrial Hygiene, Vo 17 21, pp', 3B3-BiHapest, 1977.------- 5515. Anderson, D,, etal. "Chromosomal Analyses in Vinyl Chloride Exposed Workers: Comparison of the Standard Technique with the Sister-Chromated Exchange Technique, Mutation Research, Vol. 83, pp. 137-144, 1981. 5516. Busey, W., "Pathology Report on the Brains from Mice, Hamsters and Rats Exposed to Vinyl Chloride in the Industrial Biotest Study 663-03222", Experimental Pathology Laboratories Inc., Herndon, Va., May 14, 1980. 5517. Wheeler, R. N., et al. "Properties and Essential Information for Safe Handling and Use of Vinyl Chloride", Control Technology in the Plastics and Resins Industry. HIOS'H, 1979.---------- ------------------- -------------------------------------------------------L 5518. Chemical Safety Data Sheet SD-56 Vinyl Chloride, Manufacturing Chemists Association, Washington, D.C., 1972. 5519. Detection and Prevention of Industrial Chemical Carcinogens Workshop - Vinyl Chloride Model. University of Lousiville, Health Science Center, 1976. 5520. Vinyl Chloride Monomer, P.P.G. Industries, 1977. Second Supplemental List includes items missing from other lists that could be identified. RNW 6/28/84 UCC 070664