Document weO4DJ7Gpkb0LmMLjXwmb52B

% " f- -- MAY 14 1975 U.S. CONSUMER PRODUCT SAFETY COMMISSION WASHINGTON. O.C. 20207 May 6, 1975 Dr. Theodore R. Torkelson Corporate Medical Department The Dow Chemical Company Bennett Building 2030 Dow Center Midland, Michigan 48640 Dear Dr. Torkelson: Thank you for your letter dated April 23, 197S, regarding CPSC*s proposed protocol for inhalation studies on vinyl chloride. As 1 remember, you have a copy of the original protocol scheduled to be performed at Edgevood Arsenal. Attached is a copy of the proposed changes. In regard to the schedule, the .acute study of 1 hour only with rats and mice and bolding for 24 months is now in Its second month. The three generation reproductive studies are now in the 60 day exposure stage. The sub-acute inhalation stage is entirely new and is just beginning. If I can be of any further help, do not hesitate to call or write. Attachment Robert M. Hehlr, Ph.D. . Director Bureau of Biomedical Science ASV 0QISqq -ONSUMER PRODUCT SAFETY COMMISS. .1 During a visit Co Biomedical Laboratory by Drs. McLaughlin and Wyer on 27 March 1975, It was mutually agreed by the contract project officer. Dr. McLaughlin and Dr. McNamara, Edgewood Arsenal Contract Administrator, that Che following technical changes would be made In the toxicological testing of Vinyl Chloride monomer: 1. No biochemical or enzymatic work would be performed in the vinyl chloride studies. 2. The three generation reproductive studies will be changed as follows: a. The number cf animals per dose will be Increased from 10 to 25. b. The exposure concentration and time of exposure will be 50 and 500 ppm, 5 days week/10 weeks. c. The parent generation will be held and observed for 2 years. d. No teratology studies will be performed. 3. A sub-acute Inhalation study will be added to the acute work. The exposure schedule Is as follows: Dose level 50 500 Control Sub-Acute Vinyl Chloride Inhalation Study (Exposure Schedule) . Species (Strain) Number Exposed Frequency of Exposure Rat (Fisher) Mouse (A/J) 180 5 dy/wk - 20 wks 180 n ia Rat (Fisher) Mouse (A/J) 180 5 dy/wk - 2 wks 180 it it Rat 50 ppm 500 ppm 100 100 _-- ---- Mouse 50 ppm 500 ppm 100 -- 100 - - i i r RSV 0001501 t The observation and sacrifice schedule is as follows: Sub-Acute Vinyl Chloride Inhalation Study (Observation and Sacrifice Schedule) Dose Level (pp=) Time of Observation & Sacrifice (Months) 8 Rat Mouse 16 Rat Mouse 24 Rat 50 20 20 500 20 20 Controls 50 ppm 10 10 level 500 ppm level 10 10 Totals 120 20 20 20 20 10 10 10 10 120 20 20 20 20 10 10 10 10 120 20 20 20 20 10 10 10 10 120 50 50 50 50 30 30 30 30 320 Total Animals: Rats - 560 Mice - 560 House 50 50 50 50 30 30 30 30 320 RSV 0001502 CHEMICAL ENGINEERING PROGRESS September 197S COOEN CEPRA 9 Volume 71. No. 9 Vinyl Chloride Emission Control Measuring and Improving Productivity-- The Discussion............................................................. How should a company tram its engineers? Should engineers set their own proieet goals, or should the company do that ? What is the best way to motivate engineers? 21 Two Engineering Meetings Focus on Engineering Cooperation.......................................... Photos from the WFEO meeting in Tunisie and from the VI Interamencan Congress of Chemical Engineenng in Venezuela. 29 LA. Meeting to Consider Energy. Environment. and Economics............................................................. The Institute and the Alpha Chi Sigme Lectures form psn of AlChE's 68th Annual Meeting program. 91 Vinyl Chloride Emission Control * VCM Reduction and Control............................... Until a monomer-free PVC resin becomes a com mercial reality, the aspnator system should provide economical removal of VCM for dry Mend opera tions. 41 * Control Methods for Vinyl Chloride.................. Some tips on how PPG handles sample collection and analyses of VCM. and on how it handles the tricky aspect* of loading operations. 46 Control of In-transit VC M..................................... The only certainties regarding VCM regulations are that they are here to stay, and that industry wiH have little to sey concerning employee safety and plant procedures. 48 * Stripping VCM from PVC Resins....................... Here's a progress raport on a stnppmg technique that can be used in the production of resins by the suspension process. 54 Emergency Isolation Valves for Chemical Plants............................................................................. An emergency isolation valve may coat 96.000 to install, but it may prevent e fire that would be 1.000 times more costly. 93 Economics of Ethylene Glycol Processes............ A review of current technology indicates a nearterm shift to liquid-phase acetoxyiation. and for the longer-term, a move to synthesis gas derived processes. 72 The Flixborough Disaster.......................................... The Flixborough Works explosion, which was equivalent to the force of 15 tons of TNT. killed 28 people, injured 89. and damaged 1.821 houses. 77 Basin Fermentor for Single Call Protein............... Single ceil protein may be one way of feeding the world's billions. The basin fermentor may be an in expensive way to produce large amounts of single ceil protein. 88 -l^T- departments:^ Books... Lenars ... Speak Out Trends ... 2 Institute News.......... 4 People......................... 36 What's New.............. 37 Oats Service............ 103 Future Meetings .... 106 Professional Services. 108 Advertisers Index ... 119 News and Notes........ 130 148 149 ISO Editor A Publisher Larry Rteen Managing Editor John Howe Associate Editors Claudia M- Caruana Waldo B. Hoffman Publications Director F. J. Vn Antwerpen Art Director Louis H. Dufeuit Editorial Assistants Elizabeth A. Cannon Ann Rusicks Pnduction/Sole* Service Manager Frank Griaoii Advertising PndufiM 4itiibiu Abigail Miranda Recruitment Advertising Coordinator Gloria Lambaon EDITORIAL SOUNDING BOARD Frank Cozzarelli Union Carbide Corp., New York, N.Y. Warren C. Fisher FMC Corp., New York. N.Y. Howard Kehde Dow Chemical, USA, Midland, Mich. Paul Scavenger Dorr-Oliver, Inc., Stamford. Conn. CHEMICAL ENGINEERING PROGRESS (Vol. 71, No. 9) RSV 000X503 September 1975 1 Reprinted from the Archives of Environm t Health July 1975, Vo!ume31 Copyright 1975. American Medical Association Vinyl Chloride Exposure in a Controlled Industrial Environment A Long-Term Mortality Experience in 594 Employees Marvin Gerald Ott, MS; Ralph R. Lan^ncr, PhD; Benjamin B. Holder, MD Vinyl chloride ha* been associated recently with findings ot angiosarcoma In animals and man. The present study examines the mortality experience of indi viduals occupationally exposed to vinyl chloride and lesser amounts of vinyildene chloride and other compounds. Employees were grouped into four exposure categories according to the highest levels of vinyl chloride exposure A new clinical entity associated with vinyl chloride exposure, acrooeteol' sis, was reported in the United States by Wilson et al in 1967.' This was elaborated by Cook et al,- Dodson et al," and Dinman et al.r In 1972, an environmental study of vinyl chloride workers by Kramer and Mutchlei- revealed laboratory indica experienced for at least one month. tions of liver disease in workers Although no angiosarcomas were found and there were no deaths due to any liver malignancy, the observed mai. deaths exceeded the expected among workers In the htgfvexposure category. Fewer than expected malignancy deaths were observed in the remaining exposure categories. exposed to a time-weighted average concentration for an eight-hour Hay (TWA) of 300 ppm or above, i' . of other effects associated with expo sure to high levels of vinyl chloride wore summarized by Mar-stellar and Juhe" in the European literature. Neoplasia was first associated with vinyl chloride in 1971 by Viola et al.'" Maltoni" later reported malignant changes in animals, including angio- Vinyl chloride has a 30- to 40-year history of industrial use. Until sarcoma of the liver. Creech and Johnson'1 supported this observation by recently, it was thought to be a relatheir report of angiosarcoma of the tively benign material and, in fact, liver in vinyl chloride workers. In May was once considered for use as a 1974, Tabershaw and Gaffey11 re surgical anesthetic. Reports docu leased their industry-wide epidemio menting anesthetic effects in animals logical study of vinyl chloride workers and humans and liver injury in ani that suggested increased numbers of mals from chronic exposure were malignant neoplasms at other body published in 1960 thru 1963 by Mastro- sites. matteo et a!,' Toskelson et al,-' and This report summarizes the mortali Lester et aL' ty experience of an industrial popula tion exposed to vinyl chloride in an environment for which many years of Submitted for pahiiation Auk 31, IV74; reepted Feb I97S. From ih Do* Chemical Company, Midland, Mich. Reprint reqociU to the Dow Chemical Compa ny. Corporate Medics] Department. 3X10 Dow Center. Midland. Mt 4XU0 (Mr. Out monitoring data are available. Many of the employees were also included in the Tabershaw and Gaffey report; however, in the present study the mortality experience was combined with more clearly defined levels of exposure and follow-up of former company employees. HISTORY Research involving vinyl ehloridt started at this company location in the mid-1990s. In 1941, a small copolymer plant was constructed that employed four operators, two miller-packagers, one foreman, and one superintendent. In the late 1940s, the plant capacity was enlarged and two assistant opera tors joined the work force. Th* mer plant continued to grow and other types of copolymer were developed, which resulted in a larger department with a new group of operating, cleri cal, and supervisory personnel. A small production unit to produce vinyl chloride monomer and a copolymer semiplant also were operated during this period. Continued research resulted in a new outdoor homopolymer (PVC) and copolymer unit being constructed in 1952. The rapid development of the market for PVC resin in the 1950s outstripped the new plant capacity. In response. PVC production was begun in a portion of a third copolymer unit that had previously used only limited quantities of vinyl chloride. Thus, besides the research efforts and mon omer production, three polymer units were in operation. The PVC was pro duced until 1969, when the decision was made to discontinue production of homopolymer and use the facilities to modernize copolymer production. The modernization allowed the closing of the plant built in 1941. Arch Environ Heatth/Vof 30. July 1975 Vinyl Chloride Exposure/Ott el al 339 RSV 0001504 C'C. ; J.-j: -: kC ( iltC l\ ] M Wt*. V4k I*. MVjC-SW. hr^MM PNU IHU ^l*M^ I* ClM UdlMI RLa.Aif. Gas, v \Y+M. COMPARISON BETWEEN IN VITRO TOXICITY OF POLYMER AND MINERAL DUSTS AND THEIR FIBROGENICITY J. A. Stylls and.J. Wilson Imperial Chemical Industries Limited, Industrial Hygiene Kewurch Laboratories* Aldcrlcy Park, near MccdcsticiJ, Cheshire Abstract---The cytotoxicity of a variety of polymer dusts to suspensions of rat alveolar ami (VriMRC.il ttucr^jphaye* in culture was measured using trypatt blue a* an indicator of cell death. Suspensions nt' the scute dusts were administered tu rats by intraperitoneal injection a.tj the tissue reaction wv.mmcd at I month and 3 months. A gtod correlation was found between the eytoiovieiiy of the dusts to nuerophage* in culture and the degree of fibrosis caused by them in the animals. . .. ' V. < INTRODUCTION Tne relationship between cytotoxicity of mineral dusts to macrophages in ritro and their fihrogerte activity in vivo was examined by Marks 1-t al. (1056) using a quantitalive in vitro technique (Marks and Mason, ly)S6). Further work was carried out by Conning et al. (1071) who compared the ability of several mineral and polymer dusts to prrvJuor* progressive or persistent fibrosis after imraperiioncaJ or intratracheal injection in rats, and their cytotoxic activity in rut alveolar and peritoneal macrophages in culture. They were able to distinguish three distinct levels of cytotoxicity in vitro which related directly to the degree of fibrogcnicity of the dusts in vivo. The dusts of low cytotoxicity did not cause persistent fibrosis; those of intermediate cytotoxicity were comparable to silica in their ability to cause progressive fibrosis. Only asbestos was placed in the third category* of cytotoxicity and this produced the most fibrosis. ThcTesults of these investigations suggest that there is a direct relationship between cytotoxicity of a dust to macrophages in culture and fibrogcnicity in the living animal. With the limited material available they were unable to elucidate the clVecix of changes in particle si/e and configuraticn. Marks or al. (1956) examined only mineral dusts, and Conning vt al. (1971) examined two mineral and two polymer dusts. The present study examines the relation between cytotoxicity to macrophages in culture and the lihrogcnic activity in vivo of a much wider range of polymer ami mineral duels allowing more general conclusions to be drawn. . ;/ . , - MATERIALS AND METHODS Animal.* Specific pathogen free albino Wisrtar rats (AUcrlcy Park strain) of both sexes and of a weight range 200-250 3 were used. 241 o. RSV 0001505 r