Document zQaZy6Vyn8MB2GoaDxGGjRqYn

May 21, 1973 INFORMATION ON VINYL CHLORIDE TO BE PRESENTED ORALLY TO NIOSH I. Description of the Vinyl Chloride and Polyvinyl Chloride Industry Vinyl chloride is a commodity used in very large quantities to make polyvinyl chloride resins (polymer and copolymer). The following estimated figures for 1972 illustrate the tremendous importance of this industry which has operated for 35 years in the United States and 40 years in Europe. U.S. Production U.S. Capacity World Production Vinyl Chloride 5.2 billion lbs (0.65 exported) 5.9 billion lbs 22 billion lbs Polyvinyl Chloride 4.4 billion lbs Annual growth last 5 years Projected annual growth, U. S. U.S. Plants U.S. Workers World Workers 14% 11% 14 1500 10,000 37 (23 companies) 5000 Virtually all (>99%) vinyl chloride is used in production of polyvinyl chloride and other polymers. It is difficult to estimate the number of workers employed in converting, molding, and fabricating these polymers but it is of the order of 10's of thousands, working in thousands of plants. It has been estimated that the wholesale value of fabricated products is over $3 billion. Almost all of the vinyl chloride and polyvinyl chloride producers in the U.S. are participants in the MCA Technical Task Group on Vinyl Chloride Research. Over 95% of the DTH 000011667 repeatedly exposed day after day, without adverse effect." In 1963 the ACGIH modified their recommendation so that 500 ppm was to be a maximum concentration (or ceiling) rather than a time-weighted average. This change was in part due to the publication by Torkelson, Oyen, and Rowe (American Industrial Hygiene Association Journal Vol. 22, p 35.4, 1961) of the results of six-months repeated inhalation studies on laboratory animals. These authors reported slight reversible liver injury in rats exposed 7-hours per day to 100 ppm and recommended that the timeweighted average exposure of workers not exceed 50 ppm. However, this recommendation was not considered appropriate by Lester, Greenberg, and Adams (ibid. Vol. 24, p 265, 1963) who did not consider significant injury to have resulted in rats which they had repeatedly exposed to 500 ppm v/v. About 1963-1964 reports appeared in the European literature describing pain and tenderness in the fingers of polyvinyl chloride workers. X-ray examination showed that the bones of the hand were dissolving. This condition known as acroosteolysis was also investigated by American vinyl and polyvinyl chloride companies and similar disease was found in workers who cleaned polymerization vessels. The epidemiological data from this investigation was published in January 1971. (Archives of Environmental Health, Vol. 22, pp 61-91, 1971). This epidemiological study was directed at workers currently employed by the companies. In May 1970, Dr. P. Luigi Viola, an Italian physician, reported in Houston that he had attempted to create a bone condition in rats similar to human acroosteolysis. (Tenth Inti. Cancer Congress, Houston, Texas, May 22-29, 1970). Dr. Viola observed tumors in the ear canals of rats exposed to 30,000 ppm (3%) vinyl chloride vapor 4 hours per day for 12 months. Viola also reported tumors in the lungs and bones of these rats but these later tumors are of questionable significance. DTH 000011668_ These data were subsequently published (Viola, P. L., Bigotti, A., and Caputo, A., Cancer Research 3^, 516-522, May 1971). In 1970 the ACGIH proposed reduction of their recommended TLV to a time-weighted average of 200 ppm primarily on the basis of work reported by Kramer and Mutchler at a 1968 Gordon Research Conference on Toxicology and subsequently published in January 1972 (American Industrial Hygiene Association Journal, Vol. 33, p 20, 1972). The authors reported evidence of clinical findings in workers exposed to a time-weighted average concentration of 300 ppm VCM for many years. In 1972 the ACGIII took vinyl chloride from the list of Intended Changes and changed the value in their regular list to 200 ppm. This value remains the recommended value in the 1973 list. A copy of the Documentation for the ACGIH TLV for vinyl chloride as published in 1971 is attached. In order to get more details of Dr. Viola's experiments, including additional unpublished studies and observations that he might have compiled, he was invited by the Manu facturing Chemists Association to visit Washington and discuss his findings with MCA's Occupational Health Commit tee. On May 5 and 6, 1971, he discussed data published in 1971 and referred to other studies completed and underway. Dr. Viola was extremely vague and evasive in giving details. He did report that his vinyl chloride was quite impure and claimed to have seen tumors in rats exposed to 5000 ppm. He thought 2500 ppm would be without such an effect. He produced no data and refused to give details. He "claimed ' he would not be concerned about workers exposed to less than 500 ppm. We are not aware of any further publications by Dr. Viola on this subject. DTH 000011669 DOCUMENTATION OF THE THRESHOLD LIMIT VALUES FOR SUBSTANCES IN WORKPOOM AIR - Third Edition 1971 VINYL CHLORIDE CH2=CIIC1 200 ppm (Approximately 770 mg/m^) Vinyl chloride is a flammable gas with anesthetic properties at high concentrations. At anes thetic concentrations (8 to 12%) it has serious effects on cardiac muscle resulting in arrythmias and sensitization in dogs(l,2). There is a wide margin between anesthetic and lethal concentrations (30-40%)(3). Torkelson, Oyen and Rowe(4) reported that repeated seven-hour exposures for six months at 200 ppm resulted in histologic changes in the central lobular region of the livers of rabbits, but not in rats, guinea pigs and dogs. At 100 ppm there was only slight liver enlarge ment. A subsequent report by Lester, Greenberg and Adams(5) on the effects of repeated ex posure of rats to vinyl chloride assaying 99 + percent purity at 2 and 5% concentration stated that, although liver changes were noted, they were not considered to be of pathological signif icance. In their opinion, a recommended TLV of 500 ppm was satisfactory for worker exposure. An interim report was made by Mutchler and Kramer(G) of long industrial health experience with vinyl chloride workers. Beginning in 1950, continuous monitoring was begun at five or six stations and the results compared with breath analvses(7) for vinyl chloride for 50 workers. Between 1950 and 1967 the mean air concentration was 160 ppm, with one maximal peak at 600 ppm of vinyl chloride and with great daily variation from 30 to 170 ppm, on the average. During part of this time vinylidene chloride* was an associated air contaminant estimated at around 5 ppm. Twenty-one clinical parameters were measured for comparison with the environmental data, and relationships were obtained by stepwise multiple linear regression analysis. Of medical examinations numbering 404 on 97 workers, 66 were used for comparison with 650 controls. These examinations with final diagnoses made according to the international classification of diseases, failed to reveal any overt condition attributable to vinyl chloride (or vinylidene chloride) ex posure. No differences of physiologic significance were found in blood pressure, hemoglobin, electrocardiograms, and no body abnormalities (acro-osteolysis) appeared.No one was clinically ill. Six clinical parameters appeared to be altered, however. Among these, beta lipoprotein. Icterus index, and bromcsulfalcin retention time may have some physiologic significance. The investigators felt, from a review of the interim findings, that a time-weighted average exposure concentration at 300 ppm (combined vinyl chloride and 5 ppm vinylidene chloride) could result in some degree of liver dysfunction. The multiphasic screening tests are continuing on all ex posed workers, and analysis of the findings is being made on an individual worker basis. In the meantime, a time-weighted average threshold limit value of 200 pprn vinyl chloride (with a few ppm vinylidene chloride) seems appropriate to prevent adverse systemic effects from longcontinued daily exposure. (* A 90-day animal inhalation exposure to vinylidene chloride at 5 ppm was without observable effect.) References: 1. Oster, R.IL, Carr, C.J., Krantz, J.C., Sauerwald, M.J.: Anesthesiol. JL 359 (1947). 2. Carr, J., Burgison, R.M., Vitcha, I.F., Krantz, J.C.: J. Pharm. Exptl. Ther. 97, 1 (1949). 3. Mastroniatteo, E., Fisher, A.M., Christie, H., Danziger, H.: Am. Ind. Hyg. Assn. J. 21, 394 (I960). *" 4. Torkelson, T.R., Oyen, F., Rowe, V.K.: ibid. 22, 354 (1961). 5. Lester, D., Greenberg, L.A., Adams, W.R.: ibid., 24, 265 (1963). 6. Mutchler, J.E., Kramer, C.G.: Report on Relation of Exposure to State of Health of Dow Chemi cal Workers, Gordon Com'., Tilton, N.H. (August, 1968). 7. Baretta, E.D., Stewart, R.D., Mutchler, J.E.: Am. Ind. Hyg. Assn. J. 30, 537 (1969). (Reprinted from American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio) DTH 000011670 III. Toxicity Studies in Progress 1. MCA-Sponsored Inhalation Studies. As announced in March of 1973, the Manufacturing Chemists Association has contracted with Industrial Bio-Test Laboratories, Inc., Northbrook, Illinois, to conduct two-year studies on rats, mice and hamsters. Groups of 100 male and 100 female of each species (600 total) will be exposed to either 0 (control), 5000 ppm, 500 ppm, or 50 ppm of vinyl chloride monomer, 7 hours per day, 5 days per week for 12 months. They will then be observed for an additional 12 months (6 months for mice). These animals will not have food and water during exposure. This "lifetime" study is designed primarily as a cancer study and will include only a limited amount of other observations. Because Viola's studies involved simul taneous exposure of food, water, and bedding, a separate group of 100 rats of one sex will receive exposures to 5000 ppm along with their food, water, and bedding. This group is included to determine the possibility that a reaction of the vinyl chloride monomer with either the food, water, or bedding results in a toxic reaction product. Exposure of these animals started in May 1973. A com plete copy of the protocol is attached. 2. MCA-Sponsored Epidemiological Studies The Manufacturing Chemists Association has contracted with Tabershaw-Cooper Associates, Berkeley, Calif., to conduct a study of the cause of death in vinyl chloride and polyvinyl chloride workers. The objectives are: DTH 000011671 (a) to compare the mortality of individuals who have worked in vinyl chloride plants with that of the general population, corrected for area, age, and sex; (b) to compare mortality patterns within the popula tion of vinyl chloride workers, based upon esti mated occupational exposure; and (c) to compare mortality among vinyl chloride workers with the mortality of other occupational groups which TCA, Inc., has studied. This study is expected to require at least 8 months for completion and reporting. A copy of the protocol is at tached . DTH 000011672