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I • 0 TOXICOLOGI' ANt) API'L1P.n (4(.cNfIACOLUr;1"• JS• :19-?62 (1978) aI i ~~IJ! EXHIBR NO.~ Abstracts of Papers for the Seventeenth Annual Meeting o` •he Society of Toxicology, San Francisco, California March 12-16, 1978 1. nCfCCtloll qr Cr1i/rNC17! (, (';l C:"iCl''r/1•-(jnll ~r::Rala /'1nrCS: O/lli, ("U/:rnJ( rl'7 ilc'S:rilS n7l11 1/1 CU+r'('O:ellr/S. !Zt,llt ill !i. .\I( \I Uu,\• )UII• C. (rL.l\L. 8nc: CIII(1111\.\ Z. T/locl('Sov. Th: LII't' Itc~car:it L:titrra:or.cs. In lanaprlls. In(;i.tn1. Thc Ldlv becttr.;ll nut:;crt ccrcCninI: nmhoJ c(^Iti.'tin: ctmCCr.lrtlion cr.ttllcnt ;`IntCS Is;tt re:C'::!t dt:ccr:^:c; iri,•t. Cn,cr':l,l: n !'urllr,l. I':.:lrn(lCnl. 16. :_3. It)':). 1hC mclhotJ tllt)%cS ;. ^ iiSCc•n•C::l ci :hC u(tClt i!tClm:a!c in ci~h: hlt(t!inC ~,nrdn`phc (S::'nrn11C.'. ^: ^ Ilr':: •:Ir,ri .^. t: tn (i !', :IUC~,lrn1,L. 1(.'lt'/I(•r:Ch:rl Cr)rl) t1t t'.' l Il1.,lr1(1 folJ CCr1CCnfr:!Unn ra^CC jl.•In '.I^^C"t :ICh%.I!Cll ('ll)li/lt' fr:tCL(`l Cr(+Rl •\r,(,:i('r inJucCtr r:l( Irt,^ I,nm'•_Cn:ItC: -..::;s irc c..c:' .. :nnotlr.t!s Ic.tc(I. 108 Itt'Cre 1UclUtt: tn (111c )r rr(•rc Stralnc. Of IhCc, .il,' nt+t riuv:r•: clt:U.•attnn ,\ntont_ :trornauc rtltru Cpr.'r.0o':dc. ~\ i f r,: ...Int: W :- ` ".Inear+ttns" SC'CCnct!. 1U"" ••tC'C 1cInC. 1\t ;t+ T.\ iO!1 ++r'!'<\'ll ,.':nl ill If: ,,:L•Crc. I I(ltcCC:: . nf tC::vC ;^ O.•.C In +,11C or n:l ,+thcr slr,lt,7t. tr: ;:cctl• :',.'.( c ur r,\ I(t;l or in T:\IQ .:(t G(,1 rc;.:C•,:nt :If:II1Cl.l!' r,r :1n(i CZII'h. :!L'1^ ,. ,I:i;r Jcr-. .;it.!,i \~.. . 1i1C (71Cli:,h! cui•%Uttllli`nl .tt.. NortC ~J•_. . ,.. ... - rr(t• lrc:(, n'i cn'r:r,r,,:(' 2 r~'i . :'~.,^ . .. •J. . . . . ... ~I'......•.r:rr('. r,l l'ilr'll1/('ll('(ll(1H,:r7C. _. C. \1' Slll t: ;tnt! S. Gru (.N. ('r -c .,.:tl I)r . Thc ^u:a~:r,.;;c Of It nr uyc ;,''nft(~nrnl. hal I`rClt t!t;nt,ln.Irn1CJ In I•:lclrrl.l. tc:nl. Drosnl^i:rir`?. ;Int! Cu't'JrCt! In(11ttn'.Ji11:+ ..!;•. hul n(+1 ill nlanlnt;t!.. Tltcrrl•wc. ntl.r r:tl. t\;`('•i.! to tc':':((Cd CnscS 0( fivc I: nrr tlti utntltnn: tt. ••crrtl •tutl/ctl It.% a tlt,nun.ln! Ic(Jt:d lC.t. Each ,o+npcmc^: '.tat tcl(Cd it lhrcC t!rNa;: :ctcl. tt/l!t 15 rnndnm•i+rct! Itt:tle r:tl~ Itir Iccil. T!t, hIL'I'CC: t!mC. cCICC:;;i nn thC hatic uf ~II!~.r~ulC !nv,:i(c It•NIIItC. CCnt:r:lllc rtyltriitl tct:r.nl l:lllt• t1t( u; h;InC !~I!;ai. 1.'.:•!tlt' ;/rci.,lrct! .,,lutlrr.c ucr'~ itt!ii;'.'tl tll Il 1 nt!'I ~:hr,:; :I nl:. :l t,(:k:k ror !n 12.IIC I111C'.'t'.'.! tlllh (I:na:;htl.l:ifntttli .tn1l IIILIII,'~nCntC':unln~ 'Ii'cC1! :t• •r'I'.inl ;tr.tr cll •\ n::l.,+l;n t+Ir:tl.•urtnC,! (hC IrcalnlCnl :tt lilC It;t'il. Ic.IC(I. ;1nu ill 1\w '.Irzln I~nt:!ICt C:Il:ll I•vr ft+l 2 tccC~.. 1ItC I,Cnt1ICC tcl;rC t,t~rlliCCtI :It (li an.! in:tic7,.! G•r II'.,: ind t!raJ imll!.ln1c I)„Inirl.utt IClh:tilly tt:t. .•. Z ui:c:! on thc h^.;c of fout crncrt:l: Irnlt!.uuc 1`Cr Itrt•c:l::nt f0nt:lit:. t!rcul Intitl.ut(t (a r fol;ll In:pl.lrl(}. ;•r^;ttlrl/ul' (tf fcr^31CC ttlll: t'nc nf tlt,•rc t1iAtJ ur;`l:trlls. :utt! pr(1I1.+rClttn (,I~ICntal;. t%ltil t`cC or :^Ore (:C.1.: i`I:Cr'tlcn"!I;lminC. 2.4't!i::^InOanrwic Sulfaiti. ani :i•I•,ntcCti tdtCrc:tc rrl rI(i:`0C:tCttl:tlltr:,: :tntl .1 v:m ~ phcat l,nCtlii :tlnc Int!u,:c:1 tlnr•,t.n:utt :~tl:a'ut ill ;hC lirct trlnl. On rt"~aut; Illt tcc~kll !,Oc:!Ite :nnt!tnnents. ln !th~ .tlcnetLa ttln~ ~r,,u'tr;a! :._:tUvC r~.Ilun.C. :Iltt! t,,,r's n/t J nitro-n•riItc,-llrtllll~r1111a IS In (lr(1~rC,s. M.I ulMv 7v IV! I.I,: L,Sn: rn ,r ........ I u, (:,, I II,., (..r +~m i ~e ~ I ) t.,Jr '"'~' .~ [...~ '~ ,f- CTR

ABSTRACTS: SEVENTEENTH ANNUAL MEETING 287 I i exposure to 207 ppm of 2•nitropropane. Hepatocellular hypertrophy, hyperplasia, and necrosis were seen in the rats exposed to 207 ppm of 2•nitropropane for 3 months. The development of hyperplastic and hypertrophic lesions of the liver in rats following 3 months of exposure to 2-nitropropane coupled with the development of frank neoplasms following 6 months of exposure indicate that 2-nitropropane is a potent carcinogen in the rat. 155. Motor Oil Antagonisnr ojthe Effects ojSO; on Pulmonary Function in the Guinea Pig. DANIEL L. COSTA and MARY O. AxtDI:R, Harvard School of Public Health, Boston, Siassachusetts. The acute respiratory irritancy of SO; can be reduced when simultaneously administered with a submicron aerosol of motor oil. Although this antagonism correlated qualitatively with the ability of the motor oil to chemically react with SO;, the reaction kinetics did not support an "SO_•scrubbing" hypothesis. Preexposure to 100 mg~m' of motor oil alone did not alter the response to 50 ppm of SO.. However preexposure to the SO.-motor oil combination negated the irritanc} of subsequent S0, exposure. This evidence and the results of sequential exposures of motor oil. SO.. and or their combination suggest that the S0; has reacted with an additive component in the motor oil to prodilce the observed protc=tion. When characteristic dilutions of the deter¢e:tt or dispersant fractions of the complete additive package were made in mineral oil only partial protection resulted. Similar results were obtained with acid-treated motor oil. The naph:hene mineral oil used as a control in this study did not protect when given simultaneously with SO.. However, some protection was observed with long-chain hydrocarbon-based paraffin oil. The differences in the protective abilities of the pure mineral oils appears to be dependent on t^e physical st: u::uce of the component hydrocarbons. This hydrocarbon•dependent antagonism may explain part of the antagonism obsened with the motor oil. No oil provided protection against the irn:ar,cy of formaldehyde. 156. Cigcre:te Smoke lnhcla:ton Studies in Inbred Syrian Hamsters. l: Methods and DOsvret!v. P. BERNFELD and F. HOMBURGER. Bio-Research Consultants. Cambridge. Massachusetts. Maie Syrian ha-s:ers of :!:e BIO 15.16 inbred strain were exposed to cigarette smoke from tobaccc. fror. C%tre. :obac:e supplement, or from blends of these two materials for up to 100 uecl.s. The anirnals inhaled smoke for 12 min twice daily for 7 days a week using a modified Waltor: re%erse smoking r:achtne. Dosages of 22 and 11°o smoke were supplied for a period of :' sec each m.in f3liov.ed by fresh air for 33 sec. The higher dosage of tobacco smoke produced rr.axmiu-% toleraole carbox} hemoglobin levels. The effects of these smoke exposures on morta!uy, body w:ights. and carbox) hemoglobin levels are outlined. The chemical composition of smoke from the modified Walton machine is essentially the same as that obtained with .on% entional analytical smoking machines. The smoke from the various types of test cigarettes used is compared and contrasted as to chemical composition. The modified Walton machine provides the expertmental animals with fresh, as opposed to aged, smoke. Using a decachloro• biahenyl tracer, deposition studies of smoke in the lungs and larynx of the test animals have been conducted and the results are described. This deposition follows the smoke delivery of the test cigarettes and correlates for individual animals with carboxyhemoglobin. 15'. Cigarette Smoke Ir.halation Studles in Inbred Sprian Hamsters. 11: Histopathological Lesions in the Respirato!1' Tract. F. HOMBURGER, K. J. PAt, E. SOTO, and P. BERNFELD, Bio- Research Consultants, Cambridge, ylassachussets, and Boston University Medical School. Boston, Massachusetts. Male inbred Syrian hamsters (BIO 15.16) exposed for 59 to 100 weeks to smoke from filtered, P,ue-cured tobacco cigarettes showed various degrees of histological changes in the larynx. These ranged from hyperplasia in almost all animals, metaplasia, d,•splasia, and preneoplasia, to C_x i K f f f"'f 042, 6•f .2

a I 28$ ABSTRACTS: SEVENTEENTH ANNUAL MEETING invasi%e carcinoma in 37% of the animals at the high-dose level. Less pronounced and generally insignificant effects were observed at other sites of the respiratory tract. The dosage regimen described in the previous abstract was used, and was more severe than that employed in our previous publication (Bernfeld et at., JNCI 53. 1141, 1974), where the same st a,a of animals exposed w smoke from the IRI reference cigarette yielded 19% laryngeal neoplasms. At a lower, half-dosage level, less extensive effects were observed and only 7% carcinomas were observed. Cigarettes were also tested containing 20, 50. and 100% Cytrel tobacco supplement. The 1004n supplement cigarettes gave no carcinomas and only minimal histopathological changes in the larynges and other respiratory organs. The changes caused by smoke from blends Nere clearly less than those observed for the all-tobacco cigarette. A dose-response effect was again found for these cigarettes. A method is thus available for qualif%ir.g the carcinogertc propcrties of cigarette smoke by inhalation. By these tests a tobacco supplement has Seen shoµn to be inactive and to moderate the activity of tobacco when used in blends. 158. Pultnonan• Pathologr in Rats fxposed to :%fori;uona Smoke for One }'ear. HARRIS ROSF.\KRA%'TZ ROBERT W. FLEISCH.%IA\, and JoHN R. BAt;ER. SSason Resear:h. Institute. Worcester, Massachusetts. In a previous 87-day study of the effect of marijuana smoke in rodents, focal pneumonitis characterized by aggregates of alveolar macrophages M as discerned (Toxicol. .{ pp,. •Pharm,acof. 34, 467, 1975). In this 1-)ear inhalation study in Fischer rats, emphasis was placed on monitonng exacerbation or reversal of the lung irntation, defining cellular elements in,,olved in the pneumonitis and relating the toxicity to plasma THC levels. Groups of 10 rats were giver. a dailN exposure to 5. 8. or 15 puffc of marijuana or 12 pufTs of placcbo smoke or were sham- trea:e:L The smoking apparatus automaticall% provided a 50-m1 puT from each of t;:ree cigarettec in a:-sec period %%hich was retained for ?0-sez fol!owed by a?0-sec purge Kith fresh air each m:nute. Estimated J" THC doses Merc 0-1. 0 R. and 1.5 mg'kg which Nere reiated :e carbur>hemuglobm levels of 15, 30, and 51",. and plasma THC le%:ls of 58, 156. and :?» ng~ml. THC Joses were similar to those of man based in bod) surface area (0m.c k€? The b:phasic response of CNS inhibition and stimu'a:ion follo%%ed b} toierance de%:,.p-en: W as seer, in the first and fourth months. The numbers of pr.eumonitic foc; %%ere sex- and and were absent in controls. The pulmonary toxic resp,)nse to mari;uana sm.,e µas r., re% ersed during a 30-day reco% ery. 159. Studies on -he Pulntonan• Uptake of Paraquat. ALA% G. E. WtLSON, JoHN J. O'NEIL, and FREDERIK M. EyGELBRECHT, Laboratory of Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. (E. W. \'an Stee) Male Sprague-Dawley rats were intraperitoneally injected (ip) with paraquat (PQ) at a dose of 2' mg'kg and the lungs were removed 24, 48. and 72 hr later. Lung slices were then prepar:d, and oxygen consumption (QO.)and the oxidation of (1-"Clglucose Mere determined. In slices taken from different lungs the ~O; and glucose oxidation were increased, but varied by as much as 45 and 3040, respectively, whereas the variation between slices taken from control awmals was less than On. The increase in the QOt and the oxidation of 11-"Ciglu:ose was shown to be dependent on the PQ concentration in the medium. Therefore, one possible explanation of these results could be that different concentrations of PQ were present in the individual lung slices studied. The QO; in slices taker from the same lung of ip PQ animals varied by as much as 15"0. analysis of the distribution of ip ."C.PQ indicated as much as a twofold vanauon in I"CIPQ in different parts of the same lurj. This suggests that the regional distribution of PQ throughout the same lung was not uniform. Kinetic studies on the uptake of I"CIPQ into the isolated perfused rat lung (IPL) also revealed considerable variation in the amount of PQ accumulated by C T R N N ~°..) 4.; 6 . F`3