Document n9jGNKXxQROpgN1x2B3Gq6q88

R&S 111985 5P5UHSKT BSSCMSTIOH JOSH 53 *. * ." Duplicate in all cards:--p 68 69 76 / <7 $>$ 0QM343 year as-1961- File nuubar [Fight justify __ ' ' [Kuseric only] 77 78 Sub-la dea: Cods Author (s), as Last Kane PS (l?o Punctuation) and coden for journal as JAKA preceeded -by. one blank space 1 ' 20*"21 40 41 ~ 1 I -` f . I 1 1 SI 62 11 12 13 * * * ,* ** * Title of Fetort: end with space--hyphen-hyphen-space. Follow with Indeg Terns separated iron each other with -coma-space. Avoid other punctuation] ~ do'not abbreviate* 12 61 '62 ^C.K-/y,.'^y/i / G-n cl "A;_,/<. J cfjsL'r^;^ r zA*.c'-.*{ (It, y C_J" + rcj-n 7*1 22 23 24 Source (Journal, Vol., Kuabef, Pages, Date) x2 . / /C~C .......... ! in! <_ ,5?/. * 'nr <cl Mj /9 "763- ^ r* 'J \f-art ^ / 1 61 62. 31 32 Srief Sunnatr" L2 10 aWIAXY: 61 62 61 62 63 64 /is S'**'?7? PHARMACODYNAMICS AND UPTAKE OF VINYL CHLORIDE MONOMER ADMINISTERED BY VARIOUS ROUTES TO RATS Jim R. Withey Toxicology Division, Bureau of Chemical Safety (Foods), Health Protection Branch, Ottawa, Canada 0000343 Finding at least 2-3 ppm and occasionally as much as 10-20 ppm of vinyl chloride monomer in a wide range of foodstuffs has prompted concern for a possible human health hazard. The recognition of vinyl chloride as a carcinogen to humans in April 1974, following the discovery of angiosarcoma as the cause of death in at least 25 workers who had 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 on indwelling jugular cannula were dosed by intragastric intubation with aqueous solutions containing up to 2.0 mg/ml vinyl chloride. Time-concentration curves were obtained from sequential samples of blood. The uptake of vinyl chloride by this route was found to be extremely rapid; peak concentrations were achieved less than 10 min after administration of the dose. Lamination from the blood compartment appeared to be biexponential. Studies with the same animal mode! in a single restraint cage that allowed a "head only" exposure to concentrations of vinyl chloride up to 7,000 ppm in the gas 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 rales of vinyl chloride from the blood compartment were also determined from the blood concentration data after the administration of an intravenous dose of aqueous 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 part at the 14th Annual Meeting of The Society of Toxicology, Williamsburg, Virginia, March 9-13, 1975. It is a pleasure to acknowledge the technical assistance ol Mr. Peter Collins in this work. The interest, skill, and dedication of Mr. Henry fames, who surgically prepared the animals used in this study, is also appreciated. Requests for reprints should be sent to )im R. Withey, Toxicology Division, Bureau of Chemical Safety (Foods), Health Protection Branch, Ottawa, Canada. 381 lournal of Toxicology and Environmental Health, 1:381-394,1976 Copyright 1976 by Hemisphere Publishing Corporation