Document QaDadbVDDb8r6KeJjB198p25

i>/f^ manufacturing chemists association 182S CONNECTICUT AVENUE, N.w. WASHINGTON, D. C. 20009 (202) 483-6126 RECEIVED JUL 8 1974 DAVID A. WEINSTEIN WW DEPARTMENT June 28, 1974 RECEIVED Jill. 31974 P.J, JOSENHANS. To: Technical Task Group on Vinyl Chloride Research Subject: Dr. Keplinger's Testimony*at OSHA Hearings, Wednesday, June 26, 1974 Gentlemen: Distributed herewith are copies of the subject testimony which was presented at the OSHA Hearings as a portion of the Society for Plastic Industry's witness panel. Sincerely, / Kenneth D. Johnson, Ph.D. Secretary Technical Task Group on Vinyl Chloride Research KDJ/mb Attachment 51 MX BOR 009519 toxicology ENVIRONMENTAL SCIENCES CHEMISTRY plant sciences MEDICAL SCIENCES bio-test 1810 FRONTAGE ROAD NORTHBROOK. ILLINOIS 60062 Dm. ,,, . June 20# 1974 AREA COOC 312 TELEPHONE 272*3030 Mr. Jerome H. Heckman Keller and Heckman 1150 17th Street, N. W. Suite 1000 Washington, D. C. 20036 Dear Mr. Heckman: Enclosed is a copy of the testimony I propose to be made to the Occupational Safety and Health Administration on June 25, 1974. Sincerely yours. MLK/kjl Enclosure cc: Dr. K. Johnson/-" Dr. T. Torkelson / 'r* M. I*. Keplinger, Ph. D. Manager, Toxicology BOR 009520 jjadMitiial B I O "TEST latonied, 9*t> TESTIMONY FOR OSHA HEARING ON VINYL CHLORIDE MONOMER My name is M. L. Keplinger. I am presently employed at Industrial BIO-TEST Laboratories, Inc., Northbrook, Illinois, as Manager, Toxicology. I am here today at the request of the Manufac turing Chemists Association (MCA) to describe the chronic inhalation studies on vinyl chloride we are conducting under contract to them. The research I will describe is supported by the voluntary i contributions of thirty-one VCM/PVC producing companies. It is administered by MCA, with the advice and guidance of a technical panel of scientists from the sponsoring firms. Industrial BIO-TEST Laboratories is an independent consulting laboratory. I am a toxicologist whose experience includes research and teaching at the Center For Toxicology, University of Miami Medical School, Miami, Florida for 8 years; toxicologist, Corporate Medical Department, Hercules, Inc. , Wilmington, Delaware, for 4 years; and, toxicologist. Industrial BIO-TEST Laboratories for more than 6 years. I have had considerable experience in all types of toxicology including Industrial Toxicology. BOR 009521 Jnominal BIO- I C a I J.a<K>miaUe4-. y*ic. At the 10th International Cancer Congress, Houston, Texas, May 1970, Dr. P. L. Viola, of the Regina Elena Institute for Cancer Research, Rome, Italy, reported 30,000 ppm VCM exposures at fourhours-a-day, five-days-a-week for a year, caused cancers of the skin, lung and bones of rats. Professor D. C. Maltoni reported that rats exposed to vinyl chloride monomer at concentrations ranging from 250 ppm to 10,000 ppm showed Zymbal's gland carcinomas, nephroblastomas, and hepatic angiosarcomas. Rats exposed to 50 ppm did not have tumors. Under my direction at Industrial BIO-TEST Laboratories, a study is being conducted to determine the effects from inhalation of vinyl chloride monomer to rats, mice and hamsters. The protocol for the study was designed by the Manufacturing Chemists Association. The study was designed as a life-span study in these species which means 1-1/2 to 2 years for the "in-life" portion, with tissue examination of pathologists and data evaluation to follow this period of time. It was anticipated that the total time of the study would be about 2-1/2 years. The exposures of the animals was started on September 10, 1973, (which was about 9 months ago); therefore, the data to be presented are only partial results of a study which is in progress. In fact, the study is still in progress and is planned to continue. The final results are anticipated to be available about December 1975. BOR 009522 4 %uLut\ial BIO-TEST /.a&viato-'^l, 9nc. 3 In this study which was designed to complement Maltoni's studies, 200 rats, hamsters and mice (100 of each sex or 600 animals total per exposure group) are being exposed to 50, 200 or 2, 500 ppm vinyl chloride vapor 7 hours per day 5 days per week. Mice will be exposed for 9 months and kept for an additional 9 months. Rats and hamsters will be exposed for 12 months and kept for an additional 12 months. The rats are COBS Charles River; mice are CDI Swiss Charles River; and the hamsters are Golden Syrian from the same source. Food is removed during exposure, water is present and no bedding is used at any time. All 600 animals per level are exposed in a single chamber. The chambers are operated under dynamic conditions. The chambers are sealed and are operated under slight negative pressure. This is done so that, in case of an accidental leak, room air would flow into the chamber instead of contaminated air flowing out of the chamber. The concentrations in the chamber are analyzed using gas-liquid chromatography. An automatic sampling device allows samples to be drawn from 3 locations in each chamber. The concentrations at all loca tions in each chamber are monitored every day during the total period of operation of the chamber. Therefore, data are available to substantiate that the concentrations of exposure of the animals are accurate and as reported. BOR 009523 4 Moribund and dead animals receive gross autopsies and gross lesions are photographed. The major organs of all animals are fixed for histological examination. Only the tissues from a few animals have been examined histologically so far. Preliminary examination of tissues from mice which had died after about 6 or 7 months of exposure indicated possible tumors in the livers, lungs, mammary glands and/or skin. Therefore, on April 15, 1974, the Manufacturing Chemists Association and Industrial BIO-TEST Laboratories presented these very preliminary data to representatives of the Environmental Protection Agency, Occupational Safety and Health Administration and the National Institutes of Occupational Safety and Health. At the present time, tissues are still being examined and evaluated from these animals and some that have died subsequently. While the infor mation must be considered as preliminary in nature, it is being presented. The following table shows the results to date (after about 7 to 8 months exposure). Bor 009524 \  EXPOSURE GROUP CONTROL* 50 PPM** 200 PPM** 2500 PPM** INTERIM SUMMARY OF TUMORS IN MICE EXPOSED TO VINYL CHLORIDE FOR EIGHT MONTHS to H * K NUMBER OF MORTALITIES WITH NEOPLASMS TYPE AND LOCATION OF TUMORft ALVEOLOGENIC ADENO-SQUAMOUS METASTASIS OF ADENOMAS, ANGIOSARCOMA, CARCINOMA, MAMMARY TUMOI LUNG LIVER MAMMARY GLAND TO LUNG TOTAL MALE FEMALE 0 (7) (2) 0 0 0 0 4 13 2 2 .2 2 15 3 12 12 11 3 1 30 6 24 28 28 6 1 * 7 Male and 2 females control mice have been examined histologically. None had tumors in spleen, liver, kidneys, heart, or lung. ** Only mice with grossly visible tumors have been examined histologically Mice were exposed 7 hours/day, 5 days/week to Ul U1 ! iI 5600 srtUti+i'ltfli, ii I O ' I t i I rfliitij'iifo'Ut'i, y*K, 7 6 -- Note that no direct numerical comparisons can be made with the control groups as they have not been examined in the same way. Only mice with tumors have been examined in the exposure groups. No tumors have been observed grossly as yet in any of the control mice. In addition to the tumors in mice, a few tumors have been observed in rats and hamsters but the diagnosis at this time must be considered tentative. At this time it appears that angiosarcomas may have been observed in one male hamster and one male rat exposed to 2, 500 ppm and in one female rat exposed to 200 ppm. No tumors have been observed in rats or hamsters exposed to 50 ppm but one male con trol was found to have a dermal fibroma. These tentative data need to be confirmed and will be reported in detail when the study is completed. Since these data are preliminary in nature, conclusions from the results of the study at this time are even more preliminary. The question arises as to whether the tumors in the mice could have been spontaneous. Based on the type of tumor, particularly in the liver, and the age of the mice at this point in the study, these tumors do not appear to have been spontaneous in origin. In comparing results from mice, rats and hamsters, it appears that the mouse is more susceptible than the other 2 species. / Bor 009526