Document g2rmXGO4135nmK3n8mgaDYzjJ

/- ' / t, ^ s / MANUFACTURING CHEMISTS ASSOCIATION 1925 CONNECTICUT AVENUE, N.W. WASHINGTON. 0. C. 20009 (202) 413-6129 RELl.* IF *V III *%7. R. N. \VHEr' The attached chronology concerns attention to occupational health aspects of vinyl chloride, particularly that in which the Manufacturing Chemists Association (MCA) has had a part on behalf of U. S. producers of vinyl chloride monomer (VCM) and polyvinyl chloride (PVC). --sf This material is provided as background and for use as you wish. R&S 141400 MANUFACTURING CHEMISTS ASSOCIATION I92S CONNECTICUT AVENUE. N. W. WASHINGTON. D. C. 20009 FOR RELEASE For Immediate Release CONTACT: Richard F. Blewitt (202) 483-6126, ext. 282 VINYL CHLORIDE CHRONOLOGY R&S 141401 While it had been recognized for decades that exposure to high concentrations of vinyl chloride monomer (VCM) might cause liver and kidney injuries, the U. S. chemical industry was not aware of any cancer-related potential of VCM until May 1970. From the time polyvinyl chloride (PVC) -- the principal product of VCM -- was first produced in this country in the 1930s, the major worker hazard concern with VCM was believ d to be flammability and explosions. Controls were designed to cover these. The Manufacturing Chemists Association's (MCA) Chemical Safety Data Sheet on vinyl chloride, published in 1954, stated, "Aside from the risk of fire or explosion, vinyl chloride presents no other very serious problem in general handling. The presently accepted maximum allowable concentration is 500 parts per million (recommended by the American Conference of Governmental Industrial Hygienists -- ACGIH -- later in 1962) ... In concentrations well above 500 ppm, vinyl chloride acts as a mild general anesthetic." (more) R&S 141402 Vinyl chlorid chronology Page 2 In 1961, The Dow Chemical Company reported that long-t rm (4j to 6 months at what would correspond to normal working hours) VCM exposures of animals to down to 100 ppm VCM resulted in slight liver injuries, and recommended working exposure levels be reduced to 50 ppm. This recommendation for worker exposure was not accepted by ACGIH. In 1962, on the basis of work done at Yale University, from which the authors concluded that 500 ppm offered an adequate safety margin for human exposure to VCM, ACGIH published 500 ppm as the recommended standard. In 1971, the Occupational Safety and Health Administration (OSHA) established 500 ppm VCM as a national standard. This changed in April 1974 when OSHA, following voluntary disclosure by The B. F. Goodrich Company of liver cancer deaths possibly related to vinyl chloride exposure, set a temporary emergency standard at 50 ppm. Then, 0n May 10, citing the findings of an MCA-administered study that showed liver cancer in mice at 50 ppm, OSHA proposed a "no detectable" standard, as previously recommended by the National Institute of Occupational Safety and Health (NIOSH). The following is a brief chronology of vinyl chloride activities, relating to worker health. It is based on MCA records and input from U. S. producers of VCM and/or PVC. (more) I January 1967 August 1968 February 1970 May 1970 August 1970 Vinyl chloride chr nology Page 3 Because of reports of finger abnormalities in the early 1960s, MCA arranged for a study at the University of Michigan on acroosteolysis -- softening of finger tip bones -- among VCM/PVC workers, particularly those who cleaned polymerization kettles. Study covered clinical, epidemiological and Industrial hygiene aspects. R&S 141403 jj fi w ii w Research by The Dow Chemical Company showed slight alteration in liver function in workers industrially exposed to concentrations of up to 300 ppm VCM. Findings of the MCA acroosteolysis study were submitted for scientific publication. They appeared in the "Archives of Environmental Health," published by th American Medical Association in January 1971. The authors were unable to pinpoint the cause of this disease and recommend d animal studies be undertaken to develop an experimental model. They also recommended a worker exposure limit of 50 ppm VCM. At the 10th International Cancer Congress, Houston, Texas, Dr. P. L. Viola, of the Regina Elena Institute for Cancer Research, Rome, Italy, reported 30,000 ppm VCM exposures at four-hours-a-day, five-days-a-week for a year, caused cancers of the skin, lung and bones of rats. He concluded that "no implications to human pathology can be extrapolated from the experimental model reported in this paper." He .exposed these animals in an attempt to develop an experimental model for acroosteolysis. ACGIH considered a reduction of the worker exposure limit to 200 ppm VCM, but did not publish it as a recommendation until August 1972. (mor e) September 11, 1970 October 27, 1970 April 12, 1971 May 5-6, 1971 May 6, 1971 May 1971 July 7, 1971 Vinyl chloride chronology Page 4 In spite of Dr. Viola's study and his conclusions of no human implications, MCA's long-standing Occupational Health Committee (OHC) considered the need for additional VCM research. At the suggestion of the OHC, MCA wrot to a number of laboratories regarding the conducting of toxicological studies on laboratory animals with VCM. MCA invited Dr. Viola to visit with the OHC and discuss his findings. R&S 141404 w fV 4^ 4 a Dr. Viola came and discussed his work to date and referred to other European studies in progress. He stated the vinyl chloride used in his tests was impure. He reported tentative observation of tumors in the ears of rats exposed to 5000 ppm VCM, but gave his opinion that 2500 ppm would not produce this effect. He stated that he would not be concerned about work rs exposed to less than 500 ppm VCM. MCA's OHC recommended U. S. VCM/PVC producers sponsor animal exposure and epidemiological research on VCM carcinogenicity (cancercausing) to be administered by MCA. MCA acted on Dr. Viola's statement that other studies were being conducted in Europe and attempted, unsuccessfully, by correspondence and direct visits of a U. S. company representative, to learn of them. MCA corresponded with medical contacts of member companies, alerting them to potential occupational health problems with VCM and asked them about interest in supporting relat d research. (more) November 5, 1971 November 16, 1971 March 30, 1972 April 1972 Vinyl chloride chronology Page 5 MCA received a letter from Dr. Viola confirming observation of tumors in rat at 5000 ppm VCM (and perhaps less) and made some suggestions for further animal studies. At a vinyl chloride meeting arranged by MCA in Washington for interested TJ. S. company representatives, a European representative of Solvay et Cie. reported that he was aware of further studies just beginning in Europe. He said it was too soon to expect any data, and that he was not free to describe the source of his information nor the location of the studies. He said the exposure concentrations ranged from 20,000 ppm to 50 ppm and that groups of 25 male and 25 female rats were being exposed. He expressed concern about the purity of the vinyl chloride used in Dr. Viola's original study, since it was reported to contain one to three percent of impurities. The representative stated that Dr. Viola had observed a 10 to 15 percent incidence of ear tumors in rats exposed to 5000 ppm of vinyl chloride. Suggestions for epidemiological and animal exposure studies to be administered by MCA, on behalf of interested companies, were discussed at this meeting. Seventeen U. S. companies had agreed to financially support VCM studies. MCA's Chemical Safety Data Sheet on vinyl chloride was revised to state: "R cent research studies reported from Italy indicate that repeated, long-term high level exposures of rats to vinyl chloride, monomer vapor can result in the development of malignant tumors. However, many years of industrial experience with human exposures to concentrations frequently far abov current standards have not demonstrat d any carcinogenicity to humans." (mor ) R&S 141405 April-June 1972 August 16, 1972 November 14, 1972 December 1972 Vinyl chlorid chronology Pag 6 ^ - oO) To enable the MCA program to be design d so as to yield data of optimum significance, overtures were made by MCA to establish technical liaison with the new Europ an research mentioned at the November 16, 1971, meeting in Washington. A letter to MCA bearing this date, sent on behalf of the European sponsors, offered technical cooperation under the condition that "no disclosure of information arising from the European investigation should be made outside the individuals comprising the technical coordinating task group without the specific consent of the European group." The purposes of such restriction were (1) that preliminary indications not be released until they had been validated, thereby to minimize unwarranted speculation, and (2) that releases remain subject to the control of the project's proprietors. At an MCA meeting of company technical officials, an MCA representative who visited Europe October 19-20 reported he had obtained a copy of the testing protocol of Dr. Cesare Maltoni, director of the Institute of Oncology, Bologna, Italy, the principal investigator of the European sponsors, and was told only that results were surprising. The European group declined to release European data because agreement had not yet been reached to comply with the European group's stipulation of confidentiality. After much deliberation and with great reluctance to pledging confidentiality, the participating U. S. companies and MCA did so in an MCA communication to a representative of the European group. This was done because of the vital importance of learning of any indications from the European research, and thus having a base to proceed on further studies, if needed, without the delays which could have resulted from duplications of effort. (more) R&S 141406 I January 17, 1973 January 30, 1973 January 31, 1973 February 1, 1973 February 20, 1973 Vinyl chloride chronology Page 7 The U. S. VCM/PVC industry technical delegation visited the European sponsors and Dr. Maltoni's facilities to learn in more detail about his experimental procedures and results. 3D fla W At an MCA meeting of participating company technical representatives, a brief oral progress report on Dr. Maltoni's work was presented by those who had visited him. It was reported that, in experiments with rats, in addition to tumors of th ear canal, tumors of the kidney and liver were observed at concentrations as low as 500 and 250 ppm VCM, but not at 50 ppm nor in the controls. The European work was observed to be of high quality, similar to that which would be done in U. S. laboratories. At this meeting, it was decided by the U. S, group of participating companies to initiat an epidemiological study of VCM/PVC workers, recognized earlier as an important complement to animal testing, but most usefully carried out with the benefit of the animal research background. MCA wrote to prospective contractors regarding an epidemiological survey. Having benefited from the European study indications in setting the protocol for the MCA research program, MCA sign d a contract with Industrial BIO-TEST Laboratories, Inc., to conduct animal exposure studies. Subsequently, a press release was issued announcing,.on behalf of participating companies, animal inhalation studies with VCM that would expose rats, mice and hamsters to VCM concentrations of 2500, 200 and 50 ppm for one year, with the animals to be kept on observation for an additional year. By contractual stipulation, the study results would be made public. Four prospective contractors met with MCA to discuss the epidemiological study. (more) March 1973 April 17, 1973 June 15, 1973 June 27, 1973 June 28, 1973 Vinyl chloride chronology Page 8 g 00 MCA and participating companies initiat d steps to present the details of VCM-relat d research to the appropriate U. S. government agency. MCA proposed to meet with executives of sponsoring companies of the European project concerning the desire to make a pr sentation to the U. S. government, with inclusion of European research observations, the latter preferably presented by a representative of the European group. A date of May 9 was suggested for this visit, but it proved impossible to arrange until mid-June. Following up -on the proposal, four MCA representatives visited European group executives in Brussels. They were given assurance of the European companies' willingness to release their data -- although still incomplete -- to th U. S. government, and agreement to participate in its presentation. The European companies requested time to prepare the information for prior release to their respective governments, also. A presentation to the National Institute of Occupational Safety and Health (NIOSH) was planned for the week of July 16. An MCA press release announced an epidemiological survey, to be conduct d by Tabershaw-Cooper Associates, Inc., to document the health experience of pr sent and former* employees who worked with VCM. Again, by contractual stipulation, the results would be made public. MCA requested a meeting with NIOSH to brief the agency on the status and background of VCM research. (more) R&S 141408 July 11, 1973 July 17, 1973 Summer-Fall 1973 November 28, 1973 January 23, 1974 Vinyl chloride chronology Page 9 3J w ^ o<0 Three U. S. industry representatives reported to the MCA group the results of the Brussels visit on June 15. The European information then discussed included epidemiological data which indicat d no increase in gross mortality from cancer and no increase in cancer morbidity or incidence of cancer among workers exposed to VCM. A presentation was made to NIOSH. A summary of the published toxicity data on vinyl chloride, along with a description of the industry and full details of th studies contracted under MCA administration were presented by MCA representatives, with expressed interest in taking advantage of any suggestions NIOSH might offer. A representative of the European group (a physician), reporting on the European studies, said that tumors had been observed in rats down to 250 ppm, but that an epidemiological survey had indicat d no increase in gross mortality from cancer and no increase in cancer morbidity or incidence of cancer among workers exposed to VCM. Companies involved in the Tabershaw-Cooper survey assembled their personnel records and death certificates of employees having had vinyl chloride exposure. A further progress report of Dr. Maltoni's studies was given to MCA by a European group representative. Results confirmed earlier observation of malignant tumors in rats at 10,000, 6000, 2500, 500 and 250 ppm VCM, but not at 50 ppm. The B. F. Goodrich Company announced that Kentucky health officials and NIOSH had been notified of the company's investigation of whether cancer deaths of three workers in PVC operations in its Louisville, Ky. plant were related to occupational causes. (mor ) January 29f 1974 February 1, 1974 February 6, 1974 February 15, 1974 February 15, 1974 February 21, 1974 March 1, 1974 March 6, 1974 Vinyl chloride chron logy Page 10 Goodrich reported, in a press releas , that the death of another former mploye had been tentatively identified as due to angiosarcoma of the liver. aj MCA proposed to the European group that they make arrangements for Dr. Maltoni to come to the OSHA hearings on vinyl chloride, February 15. W _i o MCA issued a press release announcing that it had stopped circulation of its Chemical Safety Data Sheet on vinyl chloride, because of the Goodrich reports -- now questioning the validity of the Data Sheet statement noting that carcinogenicity to humans had not been observed. ^ Goodrich reported the death of a fifth employee due to liver angiosarcoma. MCA and Dr. Maltoni presented separate statements at OSHA hearings on vinyl chloride, giving background on work done to date. Union Carbide Corporation notified NIOSH of the death of a PVC worker from liver angiosarcoma. The Goodyear Tire & Rubber Company, in a press release, announced a vinyl chloride worker fatality resulting from angiosarcoma of the liver. Goodrich reported cases of liver angiosarcoma in two living employees. (more) V *# ***' * t March 22; 1974 April 9, 1974 April 10, 1974 April 15, 1974 April 16, 1974 April 16, 1974 May 7, 1974 t Vinyl chloride chronology Page 11 3J w Goodyear, in another press release, announced two more worker fatalities from liver angiosarcoma. u ^ Industrial BIO-TEST Laboratori s phon d MCA and reported that preliminary findings in the animal exposure study show d angiosarcoma was produced in mic at 50 ppm VCM MCA reported these preliminary findings to OSHA, NIOSH and the Environmental Protection Agency (EPA) by phone. MCA representatives and officials from OSHA, NIOSH and EPA met at Industrial BIO-TEST Laboratories, Inc.. Northbrook, 111., to be briefed on the findings. MCA issued a press release announcing preliminary indications that VCM exposure produced liver cancer in mice at several exposure levels, down to 50 ppm. Firestone Plastics Company, Division of The Firestone Tire & Rubber Company, in a press release, announced an angiosarcoma death of a PVC plant employee. In another press release, the results of the Tabershaw-Cooper survey wer given. The survey showed that workers exposed to VCM have experienced overall death rates from cancer that are comparable to those experienced by other U. S. industria populations, but less than in the general public. This is in spite of the now wellrecognized risk of higher incidence of angiosarcoma of the liver among such worke Also, there did appear to be suggestive dose-related increases in cancer incidence in respiratory tracts and the brain in longer-expos d workers. (mor ) > Vinyl chloride chronology Page 12 May 10, 1974 It was reported at the New York Acad my of Sciences' meeting that The National Cancer Institute had diagnosed a liver angiosarcoma in a living Union Carbide employee. The company reported this case to NIOSH in March 1974 as a liver ailment. 37 e 0) Four supplementary research projects on VCM proposed for MCA administration are now in near prospect: Rat metabolism study --4 u 44* fo Rat fetus study Animal chronic exposure study at levels below 50 ppm VCM Animal acute exposure study to test potential effects from a possible single massive release causing extremely high VCM atmospheric concentrations. ### MCA-3846