Document jBErvwjQ9g0VxNm9bZ9rdVXZQ

,-V` u CANCEROGENIC EFFECT OF VINYL CHLORIDE P. L. Viola (Regina Elena Institute for'Cancer Research) Rome, Italy Presented at the Tenth International Cancer Congress Houston, Texas May 22-29, 1970 The demonstration of oncogenic activity of some chemical ' organic compounds employed for the preparation of "plastics" has been widely investigated and the limits and the effective ness of their oncogenic power have been well defined. The present investigation*, demonstrates that it is possible to obtain for some experimental models a marked carcinogenic"" response to a monomeric precursor, i.e..vinyl chloride, of plastic polymers which follows a peculiar pattern for different tissues and organs of the rat. Twenty-six Wistar (AR/IRE) male albino rats, of the average weight of 150 gr. were exposed to vapours of vinyl chloride 4 hours a day for 5 days a week during 12 months. The animals were kept in a plastic, air-tight container through xs'hich there was a constant flow of air containing 51 in weight equal to 30.000 p.p.m., of vinyl chloride.* At the end of treatment the surviving animals were killed at twenty-day intervals and the most important tissues and organs were histologically examined by conventional methods. Twenty-five rats of the same strain were kept aside as a control. During the period of exposure the animals were slightly soporific, but the first few months of -treatment were well tolerated and the rats showed no change in body growth or behavior and no organic alterations visible macroscopically or by radiological means. 651 of the animals developed tumors of the skin and 26% of these showed tumors of the respiratory tract exclusively localized in the lungs. Very few animals developed tumors in the bone and in this case the tumors were localized in the metaphysical region of the femurs, and it is worthy to mention that the femurs of both posterior limbs showed the carcinogenic transformation. Tumors of the skin The skin transformation which developed more frequently in the para-aural region, has been the epidermoid carcinoma, but we have, seen also papillomas and rarely mucoepidermoid carcinomas. I RSV 0015993 2 Cancerogenic Effect of Vinyl Chloride .P. L, Viola Tumors of the respiratory tract Even if as far as the percentage is concerned these occur in a smaller number, their morphologic appearance is mainly of an adenocarcinoma; only in one rat it has been observed a tumor of the epidermoid type. Sometimes the tumor showed an early developmental stage and consisted predominantly of cubic or columnar cells arranged as regular or irregular tubular and papillary elements supported by poorly developed fibrous stroma. Tumors of the bones In the metaphy&ical region of the four limbs a large prolifera tion of cartilaginous tissue arises outwardly to the periostium and seems to derive directly out of the osseous cortical by the growth of its cells. The cartilagenous growth is dishomogeneous as it is shown by the extension of finger-like prolongations into the boundary of neoformed tissue. Beside the chondroblastic, chondrocytic and angiomatous areas, manifestation of noticeable growth power, there are cartilaginous zones'with regressive features, as fibrosis and hyalinosis. The results reported above indicated*that vinyl chloride is an~effective carcinogenic agent for the raT7 As for many carcinogenesis studies, where multiple tumors arise at different sites, in different tissues and organs, the data obtained need to be evaluated considering a more prompt positive response according to the ideal concentration of the carcinogenic. It is noteworthy to emphasize that the cutaneous system represents <=-an impressive pattern of susceptibility to the vinyl chloride. Another point to be considered is that all the cutaneous tumors developed in the same site, i.e., the region including the area in which submaxillary and parotid gland are located. No implications to human pathology can be extrapolated from the experimental model reported in this paper. / RSV 0015994 ABSTRACTS 81 SO SUZu 0T7*LP <> Am cc^?0;f?s* A tout W>l inhalation Study in the Rat Wlth_Od- 122 Toxicological tvaluatlon of A Conooat Pro* A Waste bater~Traatnant Plane SludieT fjjJ oaehl^^ Hw PlcMoroismcvsnurete Plhrdiets. T. menu end listens!. fMC carp., Princeton. kj. A tour Ml Inhalation toxicity study I* h*e./d#y S dayasueek) mo conducted b* exposing limit* at 1ft hU a*d 10 twlr (or* to 1.22. 20.0 end 22.4 M duet/**. the ct crmpjiinJ mo sieved prior to was to paaerete m^Ii 0(111 Umi particle il|( theft mill to inaut* better paftottetton o< Out doep lata *pe respiratory tract. Sines atoll eMy eepcaere mo iimi, pressing ty tot* probably HWltM in additional oral mula ot Out teuatniog tot i!Ui t'escceat. Typical mea oodUn dloootora tor uu dost pettlelee oaro in tba raovo 2.1 to t.S utnaturi. All eAioel* eurvisad the study. Oban camera* to untreated central enimla. tba M.4 and ll.l ag/*1 groups shomd ineraaoad incidences of dry and miat taLaa. and naoal diecbacas- aaaulta ot grans necropsy vara generally un remarkable. Maulta of olcroaeopie aaaotnatien of aalaetad ttaaaaa fion tta ttft laaol and control rata did aet raaaal any daflalta axtbemo ot oapoaata related atlaeca. CUMcal otaniatry ana orlaalyaia atwnuanwi tor all jimn fall within noraal biological Holts. A 1ft beoateiogic psreaetora nata eiaseted; hgnoglcblh (high laaal) I Muta- crlt ihltb laaal teoelsSM arycnroeyta coot laid and hlgo laaal fanalaat. neprosecd aboolata aod ralatlaa llaar vaignte In tba high ievni and alaaatod luMSbooy weight ratloa ooaaraad in Mgb laaal rata and aid laaal naUa appeared to ba tniisnt ralatad. tba no-obssrseu-rffeet laaal la ceoalOarao to ba 1.22 ag/a? in tba rat. 3. Juba*. amarlcso Cyanabld Cdmpmny, Wayne, IU; ..Poetar*. GSAC llonntci, UarabiB. HA; aod d.V. Malmltfl. PbarMSse baanareb latamatlaaal , tuerli. *. <iatt. by b. SpAraao). Tba prayer dlapbaal of waste oatar tvaatnont alui(a baa bean an loportaat cbaeora la envtxommtel piucactlod. ti- twin lataraat baa cwtarod oa the esbyoatlbg of watt activated aludge Vhlch baa cm pocaatlal of traoafbwisg sludge into a uealui Mtaxial, before each cowpoat tab gala vUaayraad appllcatlaea, tba owlrenmsitdl aataty aad wis Madllbg elwraetorldclca am ba detailed, tba prasset ecudiae address a aunbax of these considerations for a coayojt fro* Awarlcab Cyanaald'a UaUlogferd, CT. Plant, Tba conpoat vos yraparad by tba nixIn* of aludga ganaratad fro* tba secondary vnata aettvatod treat*ant ayatw with uood cblye lo aerated yXloa to produca a i;unpuat palatial TnDirr ing ca. 21 days of organic wtin dacoppealtiaa. to order to datsrwlas the acute toxicological affaeta Of the conpose oa the mwtroNtant. tba (allowing studlee vara parlor*ad and chair raspactisa twain ora indicated: Rainbow Trout LOO <9* be) >7.TOO wft> luogtU Swnfiah LCS0 (94 hr) hater Flag (Daphole wane) LC50 (19 hr) fifth Water Alga llelweatrim dOQticomuVM)~lju50 (9b hr) >7.700 a/l >100,000 ng(L >4,000 g|/l The follawlng atudtae and tbelt taauita ware uaed to nahe a health ssgssaaanC for (ha tele handling of the con peat: Acuta Oral L9S0 (rat) >5,000 ngfkg Acute Penal U50 (rabbit) ft leery Skla Xrrltaclsa (rabbit) >2.000 a/kc aisInal atyrhwa rrlnary lya Inlcatlm (rabbit) so slguiflcent efface Pbrnal Sgnaltlxaclao none Ansa iainoeaJle Hlccoaana Aeaer oob-witaganle The present rasultt And teats that chare vers so biologi cally naanlngful afinccs ic the acuta anvIrenesctel ecudiae or the Haelth ssaoasnwi taate. The coaelualen free theaa studlee. thersfora, ves that tba Wallingford Cenpoat caused >: oo algoifleenc toxicological affaeta. L fJfZAf 123 Ab-Initio 0uairt.ua Chrcietl Calculation* and Dtc- trostatlc (tolacular Potential -Waor for PradittIcq Toxicity v. Levcncnxo*. tf.s. Koskl*. and Joyce J. laufaan. Oepartatirt of ChsCiiiry, Tba Jcnn* Hopbine Unlwriity. SaltDeere, Md. 2ISIS (Intr, by Joyce j. Kaufano). Ab-lnitlo calculation* vara esrried out oc a miafotr of orgampooepoorue conpouod* using our mm program which mcorporate a uoMr of daairabla opt Iona for ab-initlo calculaticbs on larfa aolecules. We carried out ab-initio cal culations for the two optical laemrm of CB: a.C - t - (those UawTi differ lo their 3f Ngj^ toatcltiaa). Pro* tba vava fmctlone of tbe optical ismaru of Q (ealcwlaced relntlvo to internal body-fixed coordinate*) va geearatad tba elocttoatatie aolaeular potential contour aspa (relative to tba aim absolute apace-fixed reference coordi nate*} in three dlaeaeioas around each naleeula. These baba indicate vividly tba. differing stareoalectreoie rvduielte* for tba different optical Hemirs to fora eoaplexe* with aeecyieboliaodtaTaaa (ACM) and suggest tba baaia for tba cUffefbnce In tAeir io-rivo toxicltlaa. Tbeae nape for* three dlaeneiooal ataraoalactronie bdlosrnaa and cab even be ueed for revetee Inage holography to ueertaln It now, even hypothetical, noiecuie* fulfull tbe requisites. TTia tetoad pboapbOTflAtioa step of the inhibition of ACM by organepboapboru* aatltbolineetemaee of tbe icenernl fennila 0 la ralated to tba acidity of X sad to tba bond . I-.* atrangth of the p-l bond. Per aertat of com 1 i S pounds, aryl NMcthyl MatKyl pboapneranidntea. X in wbicb tbe P-X bond ia eonataat, the cuantim cnesically ealeulnted P-A total overlap population* (TDP'e) correlate tbe aapanaent-u log Iao*< for inhibition of AO> over four order* of aagnltude vlch correlation coefficient* of 0.56 tt*: TOP 0,9591; TOP'S 0,9611). This reaearch vaa aponaered by tba Office of naval Research, Siophyalca, under Cootnct aOOOlb-Bl-X-0007. aouas - Environ- aantal gelanca* Laberatofy, Hotelt Sioal School ot Madltltit. One Cuaiavs L. levy Piece. Maw York, New York 10029 Hsepisstlc sftscia of lover doves of vinyl chloride(0 con trol. 1. 10. 100. 100 and 400 pyn) and ahort-ter* exposure (4 weeks) by Inhalation have bean studied by light end elec tron vlcroAeopy 1* 220 alee. Except (or dead or seriously alek aalnels, e large *e)orlty of the eolnels weve seed- {lead at tbroa dlfferaat atsgss: (mediately after exposure. 12 weeks lstsr. and 40 er *1 vnaka after exposure. Six alee (4:400 pyn, 2: Opab) wars kept Longer than 41 weeks to ex- MIM the effaces of tba chmlcal altar a long-torn recovery period. Pulanoery tmars (slvsologsnlc tiftorg) and hepatic and aatrahapatic Amonglosercows were ioduesd in these anlnals. Alveologcole tuaora ware first observed 10 waaka attar axpeaura to 400 pM- lb the subgroups exposed to higher cobceatretleae (400 pp* and 100 ppb) tbs iwitnee of timers was higher end chair eypeerenee ves earlier than lo tbe subgroups axpaaad to lower concentrations (100 ppa. 10 and 1 ypw). These findlags Indicated a doae-respbnsa rela tionship for incidence of slvoologenic tmore, sod Che latency period vaa lavaraaly ralatad to daoe. Two hconglo- aarcoma (1 suheuteoeous and 1 bapatlc) vara also Induced in either a muss's ear 29 weeks after axpeaura to the 10 ppu vinyl chloride and a muse's liver 54 weeks after exposure to the <00 pyo vinyl tblotidx. respectively. (Supported by Research Crsnt OH 00691 fro* KIOSK). 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