Document RJrkQ9dBVj2zGNxzwg9zE8Gvv

ALBERT C. CLARK TCCVHICMKtCWALMOIDinKeMcTrtM MANUFACTURING CHEMISTS ASSOCIATION 1625 CONNECTICUT AVENUE, N.W. WASHINGTON, D.C. 20009 (202) 483-6126 August 30, 1974 George Roush, Jr., M.D. Monsanto Company 800 N. Lindbergh Boulevard St. Louis, Missouri 63166 Dear Dr. Roush: Herewith is an invoice for payment of your company's proportionate share of research programs on the metabolism of vinyl chloride and on possible teratogenic properties of vinyl chloride, in accord with your earlier commitment. These programs were recently approved by the MCA Board of Directors. As they are now in progress by The Dow Chemical Company, an early response would be appreciated. Although we now have commitments in support of additional chronic inhalation studies and a pro posed study involving a single massive exposure of mice to vinyl chloride, the final protocols have not been decided. A decision is expected soon and you will be advised accordingly. Sincerely, (/l^ ACC:tp Enclosure Bill for $1,200.00 for Monsanto's shareresearch program on metabolism and possible teratogenic properties of vinyl chloride sent to D. W. McDonald for payment on 9/4/74. RSV 0001008 ir MANUFACTURING CHEMISTS ASSOCIATION 1*2S CONNECTICUT AVENUE, N.W. WASHINGTON, O.C. 20009 {202) 4*3-6126 August 30, 1974 To: Technical Task Group on Vinyl Chloride Research Subject: Percutaneous Absorption of Vinyl Chloride Monomer Gentlemen: The Dow Chemical Company has made available to the Task Group the attached preliminary report from their company-sponsored studies on the percutaneous absorption of vinyl chloride. These data suggest that, in the rhesus monkey, although percutaneous absorption does occur, it is (if my slide rule didn't stick) less than 0.1% as rapid as the take-up by the lungs from an atmosphere of equal VCM concentration. Sincerely, KDj/mb Enclosure cc: Dr. D. P. Duffield Mr. A. W. Barnes Dr. Tiziano Garlanda Technical Task Group on Vinyl Chloride Research RSV 0001009 Ii V 1O percutaneous absorption op vinyl CHLORIDE (VCM) gas in THE RHESUS MONKEY By: R. Hefner, P. Watanabe, P. Gehring Dow Chemical U.S'.A. - Midland; Michigan The experiments described herein were designed to de termine the degree to which vinyl chloride monomer (VCM) gas (Matheson Gas Products, Joliet, 111.# 99*9% purity) may be percutaneously absorbed. A male Rhesus monkey (Macaca mulatta) weighing 5 kg was used in the experi- ment. Prior to exposure, 30 mg/kg sodium pentobarbital was administered intravenously. An endotracheal catheter with an inflatable collar was inserted into and the trachea connected to a Harvard respiratory pump adjusted to deliver a volume of 20 ml of air at a rate of 28 to 38 cycles per minute. A catheter was placed in the saphenous vein of the ' . ' _ . _ .? :-n :. -j \-?".o .. * left leg so that additional sodium pentobarbital could be administered during exposure. The body of the monkey was placed in a 191.5L plexiglas chamber with the head protruding from the chamber through a silastic rubber membrane. After the hair around the neck had been carefully removed with clippers the membrane was fitted around the neck and secured to the skin with tape, to provide an adequate seal. The body of the monkey rested on 3 large glass bell jars in the chamber. A slight vacuum . : .-.iri-iL' -;oii ns/;. - v-# - -'-r'.' -- - was pulled on the chamber, and 1.5L of VCM gas was metered in to establish a VCM concentration of approximately 7000 ppm in the chamber. Chamber concentrations were periodically monitored by infrared analysis (10.9 y). RSV 0001010 \ i i tL To trap VCM in the expired air, a polyethylene tube filled with 0.5g of carbon made from saran beads was placed in the exhaust port of the respiratory pump. A similar tube placed on the intake port filtered any.VCM.from the air pumped into the monkey. The expired air traps were changed at 1/2 or 1 hour intervals while the intake traps were changed every 2 hours. The VCM from these traps was eluted with carbon disulfide atadry Lee temperature and analyzed by gas chromatography. Additionally, a sample, of control saran carbon was checked for VCM. It was found that the VCM concentration in 4the exposure chamber declined more rapidly when a monkey was present than if empty, however, it was not possible to attribute this difference solely to percutaneous absorption. Comparison would be valid only if identical chamber conditions could be obtained. This is .not possible since an empty chamber could not be made to simulate the leakage I"? % r. 3.Jr . .. <. " : - characteristics, adsorption to fur, and thermal mixing ; : ii* -i .i:; c'.*?.;' .-.Z " T : .. - characteristics in the test solution. A nonkey was exposed to approximately 7000 ppm Cfr\rpu'' * - ? '"'* VOI (specific activity 0.180 yCi/mg) for 2 hours. .Immediately post-exposure the monkey was sacrificed and tissues (brain, -:-`r J?- ~ heart, lung, liver, muscle, stomach, duodemum, thymus, spleen, mesenteric fat, testes, kidney) were sampled and homo genized. Urine was taken from the urinary bladder and bile ~ .. -I' .* :-,.*0 RSV 0001011 from the gall bladder. Aliquots of the tissue homogenates were combusted and the ^C-COj trapped in 2-methoxyethanolmonoethanolamine solution. The resulting CO2-2methoxyethanol-monoethanolamine solutions, as well as aliquots of urine and bile were counted in scintillation cocktails using a Mark II liquid scintillation counter. 14C activity in excess of twice background was detected in only the bile, kidneys, and liver. 1792 DPM of ^4C activity was in the bile, 11,352 DPM in the kidneys, and 105,821 DPM in the liver, for a total of 118,965 DPM. Expired air samples contained a total of 182,709 DPM for the 2 hour exposure period, thus a total of 314,618 DPM or 0.024% of the VCM (3.28 g or 1,316,987,916 DPM) in the chamber was absorbed percutaneously. over the 2" hour period. Of the total dose absorbed percutaneously, 39.4% was in the tissue, while 60.6% was in the expired air. The aforementioned experimental results demonstrate that small amounts of VCM are percutaneous ly absorbed by a monkey maintained under the described experimental conditions. Assuming that the percutaneous absorption of VCM is proportional to the surface area of the body, extrapolating the amount absorbed by the monkey under the specified conditions to that which would be absorbed by a 6 ft, 90 kg RSV 0001012 man yields 4.76 109 of VCM. Possible influence of fur and clothing was not determined and,, therefore* not considered in making this extrapolation. However, this data indicates that the amount of VCM a man would absorb through the skin in an atmosphere containing 7000 ppm in two hours would be equivalent to the man breathing an atmosphere containing 0.186 ppm VCM for an eight hour working day. This theoretical calculation assumes that a 10 m^ volume of air was breathed over eight hours and all-.VCM was assimilated. RSV 0001013