Document qkrZo79rbvnwdgQ71Odz18jYk

/)! FJ CriM T<rrf Vi4 IV M) M Pi" l*?S PmaI n> (W*J* Inuit _ ? ,. wwiuiwu .iiiLiuut voor \ , PubliL^i Nr LOi^ !.%* i.. OBSERVATIONS ON THE ORAL ADMINISTRATION AND TOXICITY OF VINYL CHLORIDE IN RATS* V. J. Fmnv A. J. Smut. Mamianm I. Wiitl'MS. D. van Battlxi and A. P. t>. Gwiot tn%tiluli' for \utrttuni him/ Fimnl Rr^^rclr |CH 0\ T\0. Covc/mwvuu 4.x. Zcisf. 7 hi .\ettu-rUwits f t /p*il 19751 V " Abstract Vjnotis (visibilities were studied for admuiMcnri;! rnW chloride monomer (VCM) cr.ilK in rats L p*'i si>r.ge. volutuins of V< `M jj MH.i-rv-in oil apiv.ircd to he suhie uh f.srcei \.i their VCM content .nut the fall) acid tumpiMiii'n of the oil. In udouion no oli!*otner of vmyl cblo'nJe or reaction prodiei> *f \CM mill components of ihc oil were detected. Stomach m'rtnmpn of sae.i Mhtliom wax eor.Mikered an acceptable mellnsJ of omI .idnuuuiruiunv cl Vl'M to r.it in sho'-f-term toxicity studied Within .1 pcnoJ ot J hr iollowinc incrae.ioric nnuftitipn of VCM in s/vj-fKjn oil i Don ms Vf.M kg hodv ucigliti. i-vcr V2",, of the VOM aunimolcreil was recovered from tile ja*cs excreted (rruink exhdlcj'1 hv (lie animals Eructation did not appear to be involved in the excretion of VCM. VCM dissolved in soy.i-bean oil was administered h) gavace to male and female rats at levels of li icontrolsi. .hi Mm .nul .hv mg ku hod) weight, once daily on n days wk for ;t period of l.t wk. Several tMcnoinlogicul. hincncmieal and organ weight values differed to a statistically significant degree from those o! the controls. i*m these u<ilcrcnccs were considered t" have only minor, if any. toxicological signiirc.inec. \ slight increase m |iier-tn*biwJy weight r:.tio recurred in males and ferrules on the highest do*.- L-iei. This inere.ise wa* not accompanied hv nver damage, as was evident from histologif.n examination. enzyme Iji-Mcliemc.lry and electron tmero-eony The no-vlTcu level in (his 90-d.iy study wjs conservatively placed at Mi me VCM kg hod' weight, but was probably Ii.cIkt since the ello.iv occurring at (Ik) and JUi mg kg body weight were of doubtful toxicological significance. indications w.re obtained that the levitinc of rats on diets containing pol>vmyf chloride fPWi powder with a high V< M womcm i> .1 more practical meihod lor the long-term oral exposure of rats to VCM than is stomach intubation of VCM m nil. VCM was almost completely released from PVC powder during passage through rite digestive tract. tNTROIH (TION Certain formulations of PVC arc used widely as Vinyl chloride monomer (VCM) i used in (he manufacture of the resin, polyvinyl chloride tf'VCi. Industrial exposure to V('\| has Ivon associated with sever::! disorder, including ucro-onicoivsis iDirmnn. Cook. \\ hiiehousc. Macmison & Ditchetk. |97|; Hams & Adams l`6*': latnuc. Jiihc. -Stein &, VcU- man. 19T-1: Murkou it?. McDonald, f'cihterc .& Kcr/ncr. Id*') and noti-'t\ili*:::am liver diseases (Kramer A Mutd-ler. 1*772; MursteUer. Lellwh. Muller. Jtilie. Lange. Kolirer A: Veltr.un. 197.': Sueiu. Drejman A. Y.ilu.skai. Idfw 1 and. only recentt\. also with anei'isjreonu of the loer tliloek. 1*774: f'rcech A Johii-vv'ii, Lev A; Harry. 1974) and lomours of the hr.tut and Uttigs rNU.iiwui. Peters <k Johnson. 1974J. Degenerative vhaiiees in the iiwt. `.idnevs. bone aikl brain w VIe dctecud m rats and lahhns fol lowing evposinv u \t A| umat.!ii.n ilLtsilaev. \a/m &. Kwi-etkov. i*"I f.ieuer. keynohN, t*oi:olly. Moslen. SaiIv it Muii'hv. .`.'"d. ri'fkvlMiir. Oyen jc Rowe. |dr|; Vii*b. !'/"0i M.ir^iwr. VCM mlnlation was hntiul to uuluee '.vm'< 'ir m xtl-; rats attvl mice I97'|iM.llton; ,V l.vlemute. .974. \ ula. UicOlti A: kapuio. food-pncknainc materials. Residua! VCM present m the extruded pvlyme;ic pr<xluct was shown to be lunlc to migration into PVC-paekcd foods and drinks, especially distilled spirits Ikandolph. 197.'). Since no data on the oral to.vicny of VCN1 appeared to be avaii.thle. studies were initiated to examine the sub acute toxic properties of this compound when admin istered oraily t.' rats. Oral administration is greatly hampered by the tact that VCM is j git* at rt>otn tenifvrature tbp. r.- le b (') and therefore preliminary exjx'rtmenis were carried out to find an acceptable way of administering tiv compound orally to mis. Administration in the drink nig-waier was consi dered m this iceoccl but was reveled because of the rather pi>or solubility of VCM m water iHardv. |Vf4i ar.tl. more sigiuticantly. because <u the Jilliciiltiv's to he expected tr. Iiamlling the solutions and in cstinvttinc the vjiiuntincs of VCM actually ingested by (he animals. As VCM is lipophilic, nc inve.stiptcd the possibi lity of administering VCM as a solution m edible oti *ither by gastric nmilvition or by mcorpsiraUi.-in into the Jiet. Another iv'ssibility studied was the additu*n to tlte diet ol a PM' |\-wilvr containing an um'su.illv Tl'x siadi sas si ,.ns.iro-( b\ a env.m .f en-i'nvr.inng I Lfnp.'jn u.dusi:,e*.. i.rciti Ime V, tjiut Kun-.isiotTcr* /cuueitile Indu* <ri: - V H .ile.ai Republic of t ierm.tnv) high concern ration of VCM. The present report descnlvs leiit.itoc experiments on the 0r.1I ddimi.istration ot VCM and presents Shelf \v\!.rl.nu Cia ini ' |>ul. h Stale Mines, yk/n /out st>ine Aibsetvatwms on the fate of VCM in rats In < hetmv SvvWitwad UA and !>,* t hvmtsai I \wnjv SA. '.iddttwnv live results are given o. a snisictite toxicity ... 1 * >1 6M RSV 0012375