Document Eqq7N53zBX7JoE4ke0GwmvnB0

CRI NUMBER DOW CONFIDENTIAL INFORMATION R & D REPORT DOW CHEMICAL U.S.A. BSD REPORTS SHOULD REMAIN ON THE PREMISES OF THE DOW CHEMICAL COMPANY DEPARTMEN T Health & Environmental Science/Toxicology Research Lab. "iTm NUMBER K-un-on laboratory report code H ETiK-1711 - (31L O A T E ISSUED June 5, 1980 L A. Li. NO. PROBLEM NO. 9 ,1 ,7 0 .0.0 P .3 ,2 ,4 PULMONARY EFFECTS OF VINYL CHLORIDE. COOPERATIVE STUDY NO. 3 WITH THE MT. SINAI SCHOOL OF MEDICINE, NEW YORK, NEW YORK -RECEIVED- A u THOR IS) H. 0. Yakel AUTHOR (SI SIGN A TURE 151 FEB % 0 1981 VCM TECH CTR- PAGES IN FULL REPORT M. J. McKenna This report is: INTERIM 1 FINAL and mainly: - EW n _R_E_V_I DESCRIPTIVE SUMMARY WITH CONCLUSIONS: This study was conducted in cooperation with Dr. Yasunosuke Suzuki, Research Professor of Community Medicine, Mt. Sinai School of Medicine, New York, NY-. The study design was recommended by Dr. Suzuki after consultation with Dr. Michael J. McKenna of the Toxicology Research Laboratory and Dr. William Wagner of NIOSH. This report is limited to the methodology used and results obtained during the exposure portion of this study. cn O o <J> P. `'Ursuant -J37 Ctstna Qt Hew York DISTRIBUTION: department tiles R S. D ADMINISTRATION CENTRAL REPORT INDEX ( 566 Bldg. - M.dlond) -U COPIES fOHM C 4jCQ PRINTED It J 80 Dulfibution lilt i, conlinurd on cllached pogo* R&S 040645 PULMONARY EFFECTS OF VINYL CHLORIDE COOPERATIVE STUDY NO. 3 WITH THE MT. SINAI SCHOOL OF MEDICINE, NEW YORK, NY By H. 0- Yakel and M. J. McKenna ...... ^ Produced Pursuant i.:n -337 ' .ntOuP'/ L' -j-- - h; Western Districr q( New York Toxicology Research Laboratory Health and Environmental Sciences, USA Dow Chemical USA 1803 Building Midland, Michigan 48640 INTRODUCTION This study is a continuation of the work on "Pulmonary Effects of Vinyl Chloride" conducted in cooperation with Dr. Yasunosuke Suzuki, Research Professor of Community Medicine, Mt. Sinai School of Medicine, New York, NY. The first cooperative study was completed and is the subject of Toxicology Research Laboratory report HET-K-1711 -(27) issued July 17, 1979 entitled "30-Day Inhalation Study of Vinyl Chloride in Mice and Hamsters". Since all animals ip this study were shipped live-by air freight to the Mt. Sinai School of Medicine upon termination of exposures, this report is limited to the methodology used and?results obtained during the exposure portion of this study. p-- i. .7 R&S 040646 Test Material METHOD feo i'.V Wes/ern C:Si, - "-J. 1 - J ; II 0/ I'jew York v*aPy The vinyl chloride was supplied by the Dow Chemical Company and --- was determined to be 99.9% pure by gas chromatography. Test Animals The animals used in this study were male CD-I mice, 5-6 weeks old (Charles River Laboratories, Portage, MI):'"- All animals were randomized / from a single lot using a statistical randomization procedure generated - by a digital computer program. The mice were individually identified with a metal ear tag and acclimated to the laboratory environment for approximately two weeks before starting exposures. Body weights were taken on all mice on experiment days 0, 4, 11, 18 and 25, and analyzed by analysis of variance and Dunnett's test. All animals were observed daily for signs of toxicity as well as changes in appearance and demeanor. Exposure Regimen Two groups of animals, each consisting of 30 male mice, were exposed to 0 (control), and 300 ppm vinyl chloride. One group of 40 male mice was exposed to 600 ppm vinyl chloride. The control animals were maintained in an exposure chamber under identical conditions as the treatment groups except for the absence of vinyl chloride in the chamber. Exposures were 6 hours per day, 5 days per week for a total of 22 exposures in 30 days. 2- - Chambers, Vapor Generation and Analyses The chambers used for this study were stainless steel and glass Rochester-type, approximately one cubic meter in volume. The chambers were operated under dynamic airflow conditions with temperature and humidity controlled to approximately 70F and 50% RH. Vinyl chloride gas was metered at a controlled rate into the airstream where it was further diluted to the desired concentration. The analytical concentration of vinyl chloride in each exposure chamber was monitored< by infrared spectroscopy at a wavelength of 10.9 y. Standards for analysis were made by injecting a known volume of vinyl chloride gas into a 100 liter Saran gas sampling bag filled with a known volume of air. RESULTS The mean values of body weights for the exposed mice (Table 1) showed no statistically significant difference from the mean values of body weights for the control mice. Daily observations of the animals revealed no adverse effects other than two mice in the 600 ppm group that appeared to develop a rough appearing fur coat one week after starting exposures. Even,this effect was not observed,in one of the mice one week later and was barely noticeable in the other for the remainder of the study. The concentration of vinyl chloride in each chamber was analyzed a minimum of ten times daily and a mean analytical concentration for each exposure chamber was calculated (Table 2). On the day following the last exposure, all the mice were delivered by air freight to Dr. Suzuki. It was confirmed by a telephone conversation with Dr. Suzuki that the mice had arrived in his laboratory in good condition approximately 48 hours after leaving Midland. Written by: Reviewed by: R&S 040647 H. 0/Yakel, B.S. Senior Research Biologist Inhalation Toxicology M. JrT'McKennaT Ph'-D" / Group .Lead^na'.' "Inhalation Toxicology " 1 ,, r,n /<a37 ; i-jj S'Si fcw Ycrk -3- TABLE 1 ` VINYL CHLORIDE HET-K-1711-(31) MEAN + SD BODY WEIGHTS (GRAMS) FOR MALE MICE Experiment Day 0 4 11 18 25 Low Level 36.4+1.7 35.6+1.7 35.8+1.7 37.42.0 37.62.4 High Level 36.0+1.7 35.1+2.3 35.7+2.3 37.4+2.4 37.22.3 Control 36.0+1.9 35.42.1 35.52.2 37.02.6 36.82.5 There were no statistically significant deviationsi from control using Dunnett's test, p <0.05. R&S 040648 -4- Exposure Day 1 2 3 4 5 6 7 8 9 10 11 12 . 13 14 15 16 17 18 19 20 21 22 TABLE 2 VINYL CHLORIDE HET-K-1711 -(31) ANALYTICAL CONCENTRATIONS - TWA Date Experiment Day 2-20-80 2-21-80 2-22-80 2-25-80 2-26-80 2-27-80 2-28-80 2-29-80 3- 3-80 3- 4-80 3- 5-80 3- 6-80 3- 7-80 3-10-80 3-11-80 3-12-80 3-13-80 3-14-80 3-17-80 3-18-80 3-19-80 3-20-80 4 1 2 3 6 7 8 9 10 13 14 15 16 17 20 21 22 23 24 27 28 29 30 Low Level (ppm) 296.2 308.5 298.7 297.8 293.2 300.7 294.0 296.0 284.5 295.2 293.8 291.8 297.8 292.5 303.8 310.6 299.4 316.7 319.4 322.4 305.7 308.5 Mean SD 301.29.7 High Level (PP-m)____ 617.0 610.8 606.0 608.2 604.3 594.7 594.5 614.7 589.2 607.0 611.6 600.4 609.5 593.6 ' 605.5 602.1 603.1 602.0 595.6 635.2 599.8 590.1 6 04.3 10.3 R&S 040649 -b- TITLE OF STUDY: Vinyl Chloride- Cooperative Study No. 3 In compliance with Good Laboratory Practice Regulations, this study was inspected by the Quality Assurance Unit and the results of these inspections reported to Management and the Study Director on the dates listed below. The report accurately reflects the data generated in.accordance with the 4 regulations and standard operating procedures of the Laboratory. All data and the reports are located at the submitting laboratory. *- - - i DL lc'"'- . .. . Yrr'c Study Started: 2 Feb. 80 Dates of Inspection: 1 Feb. 80 4 June 80 Report Issued Date: Date of Report: 5 June 80 1 Feb. 80 4 June 80 W. E. Hoover Quality Assurance Toxicology Research Laboratory Health and Environmental Sciences, 1803 Building Dow Chemical U.S.A. Midland, MI 48640 U.S.A. 37 03 O O con> o DISTRIBUTION F.D. Axe, Pittsburg, CA C. R. Bearden, Granville *J. E. Betso, 1803 Building (2) E. H. Blair, 2020 Dow Center W. H. Braun, 1803 Building F. H. Braunlich, Dowell, Tulsa H. H. Brower, Houston, TX R. R. Bumb, 566 Building B. E. Burgert, 1603 Building B. G. Caldwell, 47 Building R. Caputo, Sao Paulo R. R. Carleton, Walnut Creek, CA W. L. Chen, Sarnia W. B. Crummett, 574 Building M. F. Currier, Plaquemine G. W. Daigre, Plaquemine, LA R. L. 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