Document OzB7oKEp9LRR1gedN9DByeZ6e

MANU. AC7UR1NG CHEf'/iiSiS . S30ClATi0N 182S CONNECTICUT AVENUE. N.W. V/A5<1INGTON. D.C. 70009 (702) 483-6128 Tho attached chronology concerns attention to ,i 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). This material is provided as background and for use as you wish. RECEIVED KAY 2 8 1-jfl REGISTRATION 086 HiQir* ' MANL . ACTURING CHEMISTS .ASSOCIATION I82S CONNLCriCUT AVENUC. N. W. WASHINGTON. 0. C. 20009 FOR RELEASE For Immediate Release CONTACT I Richard F. Blcwitt (202) 483-G12G, ext. 2S2 VIKVL CHLORIDE CHRONOLOGY While it had been recognized for decades that exposure to high concentratio:3 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 tine 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 believed 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 -- ACGIII -- later in 1962) ... In concentrations well above 500 ppm, vinyl chloride acts as a mild general anesthetic." (more) 067 Vinyl chloric..- chronology Pago 2 In 1961, The Dow Chemical Company reported that long-term-.,_ ,,,, ,.V---- (4i 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 bo reduced to 50 ppm. This recommendation for worker exposure was not accepted by ACGIII. 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 VC", 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, on May 10, citing the findings of an MCA-ad:ainistered 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) 06a January 1967 August 1968 February 1970 May 1970 August 1970 Vinyl chlor.chronology Page 3 Because of reports of finger abnormalities ' in the early 1960s/'MCA'arrange<T*for a study at the University of Michigan on acroostcolysis -- softening of finger tip bones -- among VCM/PVC workers, particularly those who cleaned polymerization kettles. Study covered clinical, epidemiological and industrial hygiene aspects. Research by The Dow Chemical Company showed slight alteration in liver function in worker industrially exposed to concentrations of up to 300 ppm VClI. Findings of the MCA acroosteolysis study were submitted for scientific publication. They appeared in the "Archives of Environmental Health," published by the American Medical Association in January 1971. The authors were unable to pinpoint the cause of this disease and recommended 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 Congr ss, 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. ACC-III considered a reduction of the worker exposure limit to 2Q0 ppm VCM, but did not publish it as a recommendation until August 1972. (mor e) 069 Sep tcmbcr"11, 1970 October 27, 1970 April 12, 1971 May 5-6, 1971 May 6, 1971 May 1971 Vinyl chloride chronology Page 4 spite of Dr. Viola's studyandUiis^ia*^... conclusions of no human implications, ''*. MCA's long-standing Occupational Uealth Committee (01IC) considered the need for additional VCM research. At the suggestion of the OIIC, MCA wrote 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. 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 sfai dv_ that he would not be concerned about workers exposed to less than ~500 ppm "VCM ,^****^Xr**~*- 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 related research. (more) 070 November 5, 1971 November 16, 1971 March 30, 1972 April 1972 Vinyl chlo. ic chronology Page 5 MCA received a letter, from Dr. Viola confirming observation of "tumors "in'rats 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 U. S. company representatives, a European representative of Solvay et CLe. 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 grraps 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: "Recent 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 ermericr.ce with human expesur to concentrations frequently far above current standards have not demonstrated any carcinogenicity to humans." (more) 0/1 Vinyl ehlori Page 6 chronology April-June 1972 To enable the MCA program to be designed . .so as to yield data ,of .optimua^igniXicancc, overtures were made by MCA to establish technical liaison with the new European research mentioned at the November 16, ^_fc1971, meeting in Washington. August 16, 1972 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. November 14, 1972 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, Eologna, 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. December 1972 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 c; anv 1 r* + ^ ^ HC *' * W * * to *<4 to** , ***> ^ ^ %** * ' tn **!'' '* ** * to** 1 and thus having a base to proceed on further studies, if needed, without the delays which could have resulted'from duplications of effort. (more) 072 January 17, 1973 January 30, 1973 January 31, 1973 February 1, 1973 February 20, 1973 Vinyl chlor o chronology Page 7 Jt*rj The U. S. VCM/PVC industry technical : ^'delegation visited'the European Sponsors and Dr. Maltoni's facilities to learn in mere detail about his experimental procedures and results. 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 exper ments with rats, in addition to tumors of he ear canal, tumors of the kidney and liv r 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 bo 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 initiate 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 r garciug an epidemiological survey. Having benefited from the European study indications in setting the protocol for the MCA research program, MCA signed 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 bo kept or. observation for an additional year. Ey contractual stipulation, the study results would be made public. Four prospective contractors met with MCA to discuss th epidemiological study. (more) , r\y m March 1973 ' April 17, 1973 June 15, 1973 June 27, 1973 ur.,,, , w w^ ' Vinyl chloride chronology Page 8 *' * '*'***' > MCA 'and participating Companies^initiated steps to present the details of VCM-relatcd research to the appropriate U. 5. government agency. MCA proposed to meet with executives of sponsoring companies of the European project concerning the desire to make a presentation to the U. S. government, with inclusion of European research observations, th 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_the JJ. ,S. government, and agreement ito participate in .its presentation. ^Xhe^tyrjspean^ra^anies requested time to prepare~:jftjie 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 1G. An MCA press release announced epidemiological survey, to be conducted by Tabershaw-Cooper Associates, Inc., to document the health experience of present and former employees who worked with VCM. Again, by contractual stipulation, th results would be made public. MCA requested a meeting with *'TCSU to brief the agency on the sand baciigrtua of VCM research. (more) 074 Vinyl chloride chronology Page 9 July 11, `1973 'te&tr 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 t epidemiological data which indicated no increase in gross mortality from cancer and no increase in cancer morbidity or incidence of cancer among workers exposed to VCM. July 17, 1973 A presentation was made to NIOSII. A summary of the published toxicity data on vinyl chloride, along with a description of the industry and full details of the studies contracted under MCA administration were presented by MCA representatives, with expressed interest in taking advantag 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 indicated no increase in gross mortality from cancer and no increase in cancer morbidity or incidence of cancer"among workers exposed to VCM. -/ Sumner-Fall 1973 Companies involved in the Tabershaw-Cooper survey assembled their personnel records and death certificates of employees having had vinyl chloride exposure. November 23, 1973 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 rmm. Thu 2. 7. Gee uric':'. Company announced that Kentucky health officials and NICSII 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. (more) 075 4 *. -4 ` Xi January ^29/^1974. ^ Febi-uary 1, 1974 February 6, 1974 F bruary 15, 1974 February 15, 1974 F bruary 21, 1974 March 1, 1974 *f 4 ^U4 W*1 U , <rj" -L- "5 Vinyl clilor-Je chronology Pa^c 10 ^Goodrich reported,.in a press-release^* that the ^lcath of ^anothcr~former`fbmpi ye had been tentatively identified as du to angiosarcoma of the liver. " ->Ji; . MCA proposed to the European group that they make arrangements for Dr. Maltoni to come to the OSIIA hearings on Vinyl chloride, February 15. , 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.separat - statements at OSHA . hearingson Vj-nvl^'^^.; . chloride, giving backgroundjbn V'ork^done to date. ^ V: : * r-'1*' ,, * Vi.-:-- Union Carbide Corporation notified NIOSH of the death of a PVC worker from liver angiosarcoma. , - .--.j, - . ,.** *" '. - _ --- .. . 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 r.vc living employees. (more) 0T6 March ., 1974 -- April 9, 1974 -- April 10, 1974 April 15, 1974 April 15, 1974 April 15, 1974 May 7, 1974 Vinyl c ..oridc chronology Page 11 Goodyear, in another press release, announced two more worker -fatalities from liver angiosarcoma. Industrial BIO-TEST Laboratories phoned MCA and reported that preliminary findings in the animal exposure study showed angiosarcoma was produced in mice at 50 ppm VCU MCA reported these preliminary findings to OSIIA, NIOSH and the Environmental Protection Agency (EPA) by phone. MCA representatives and officials from OSHA, lilOSH 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 5: Rubber Company, in a press release, announced an angiosarcoma death of a PVC plant employee. ' '' - -**-*- -Vs-- In another press release, the results of the Tnbershaw-Cooper survey were given. The survey showed that workers exposed to VCM have experienced overall death rates from cancer that are comparable zo those experienced by other U. S. inausirin populations, but loss th public. This is in spit the * - ^3.-- of higher i r, o: w -- -- \ *i _ ~ -s Also, there did appear to be suggestive dose-related increases in car.ccr incidence in respiratory tracts and the brain in longcr-c,\poscd workers. (more) om/ 077 Vinyl chloride chronology Page 12 May 10 ,'*1974 It was reported at^ the Mew^Tork^cLuiomyw' of Sciences' meeting that The/National: Cancer Institute had diagnosed a'-liver* angiosarcoma in a living Union Carbide employee. --The company reported this * ease to NIOSII in March 1974 as a llv r ailment. % -+vrt/ Four supplementary research projects on VCM proposed for MCA administration are now in near prospect: o Rat metabolism study o Rat fetus study ", v-rv*-" 1 -- rA* -' ' ` m+w *"**&*+ ^ o Animal chronic exposure study at levels below 50 ppm VCM ' , ' .Sri* % o Animal acute exposure study to test potential effects ` ' -C-. ' from a possible single massive release causing extremely . - i , high VC1I atmospheric concentrations. ' * rMr rMf rMr MCA-3G46 V<;~ - ij ' ii^rrtr n mm % ^n>! 0/8