Document nmy25XZNGLzjZJ2m1VvKyeeY6

PHARMACODYNAMICS AND UPTAKE OF VINYL CHLORIDE MONOMER ADMINISTERED BY VARIOUS ROUTES TO RATS Jim R. Wiihey Toxicology Division, Bureau of Chemical Safety (Foods), Health Protection Branch, Ottawa, Canada Finding at lean 2-3 ppm and occasionally as much at 10-20 ppm of vinyl chloride monomer tn a wide range of foodttufft has prompted concern for a possible human health hazard. Jht^ recognition of vinyl chloride as a carcinogen to humans in April 1974, following the discovery of angiosarcoma as the cause ol death in at least 25 workers who hod been engaged in the manufacture of polyvinyl chloride, enhanced this concern with respect to the presence of vinyl chloride monomer in foods. To assess the hazard presented by the ora! ingestion of vinyl chloride monomer, rats that had been surgically prepared with an indwelling tugular cannula were dosed by rPtragastric intuhotion with ooueous solutions containing up to 2.0 mg/ml vinyl chloride. Time-concentration curves were obtained from seaueiitiai samples of blood. The uptake of vinyl chloride by this route was found to he extremely rapid; peak cunccntrulions were achieved less than JO min alter administration nf the dose. Lamination from the Mood comportment appeared to be bitxponemiol. Studies with the same animal modeI in a single restraint cage that allowed a "head only " exposure In concentrations of vinyl chloride up to 7,000 ppm in the gui phase have shown a similar rapid uptake followed by a plateau blood concentration during several hours of exposure. On removal from the vinyl chloride atmosphere, blood levels fell rapidly to barely detectable concentrations after 2 hr. The precise kinetic coefficients that describe the distribution and elimination rates of vinyl chloride Uvm the Mood compartment were also determined from the blood concentration data after the administration of an intravenous dose of agutous or vegetable oil solution. INTRODUCTION Prior to the discovery of a connection between the induction of angiosarcoma in humans and the exposure to vinyl chloride monomer (VCM) in January 1974 (Falk ct al., 1974; Thomas et al., 1975), the U.S. Food and Drug Administration had already withdrawn their prior sanctioned use of This paper was presented in pan at the Mth Annual Meeting of The Society of Toxicology, Williamsburg, Virginia, March 9-13, I97S. It is a pleasure to acknowledge the technical assistance ol Mr. Peter Collins m this work. The interest, skill, ami dedication of Mr. Henry lames, who surgically prepared the animals used in this study, is also appreciated. Requests for reprints should be sent to |im R. Wiihey, Toxicology Division, Bureau of Chemical 5afctv (Foods), Health Protection Branch, Ottawa, Canada. 381 journal of Toxicology and Environmental Health, 1:381-394.1976 Copyright 6 1976 by Hemisphere Publishing Corporation RSV 0012374 4