Document DdG9OqjE0j641nZBMJ9MddGV4

?0TIC2: Ihie aacer.a. __ ir NRrtitt Mortality and Industrial Hygiene Study of Workers Exposed to Polychlorinated Biphenyls DAVID P. MOWN, M.P.M. MARK (OWES, MLS. nUiKneDhapivmmiamMn->-l-ana--cfHaaith, Idutadan and WaMra CMitaDMawCnnl imnv mean isr lanpiins anesy mo nmn OMdan af larradlinri, HAwrA tahmdawa mA FWdSwAha Gnabnad. Ohb 4523S ABSTRACT. Romma of MW AawaMwMiwhilMaM. anknab raadtbg Mm if*-- palyihbrbMiA ML phanyla (Kill, Ml Nadanal InadauM far Owlil Safety mM Haakfe mAMM a niiAMhw hMhi amt* wMy MiAv af KMT awrfcwa b Iwa pfema aAwra PCRa wara wad Mi Aw --OHM il afeawfeal martan, AM warkara iMliiAaA In dw wafer wara amplAyud Mr at IamI SnwadiabaiaMaf lhapfealiakwaPtBiaaiawd. Tha W <mmb af MR af Ala mm aaharM aaa OawwalaaA. aw< Sj>1kp*Ma ywra wara aaaiaaafeaad.AR mam nwrbdty aaa laaar Aaa aapaaiaA (Ml aka. n MU mpj aa aaD aa aS aa*aar awwaMfr (3> aka, a U a^J. mar- Aty ana aaaaA lar raaad aana* (4 aka. ral.lgaap.) aaA la* mao* (J aka. aa 1J7 mpj. abkaafek nakkar ptaw wMtabdMRyfepidtaAa.b ana afdw pfema draakurand inaiidfey Aaa M akakuab al M* tar aaa aba abwmd. Ika raaaka af daMfead MMaakM kygiaaa aawyi can. AaafbMk|bAaal>|aABki POLYCHLORINATED IIPHCNYLS (PCRa) an a dan n--* eenvnenee ana^eMpanajn4i|i npeeiFa immshm MwJn|kn a ivpM nnen w nmnns eMnin eiesvna is ewener* tbdy araalA PCI nWaOnaa. dw wil^n pwtial af cbor- taahMmriadfeum 31 ca 4AR. Ia maw amamIaa Awra Mm aba fcaaa mm Aa*aa af aaiAaMkiailari ky AMaA* Tlw primary m of PCRl Mm kaan aa a Ifedd baulating matarid In alactrlcd capacttora and ttlmfanaara, thartfora. Aw *aaMK patantfel tar occapaibaal aapawra hat kaan In tha manufactura and raaair of thaaa aoawanantr PolycMarkmaA btphanyb Maw <ba kaan aaaA ia kaal aachan* unka, hydraulic lyuana, vacuum pumpa, paa Awnmnalon Baklnaa.ptalclaaw.idkaiNaa.panlrlAaMtMAAi.pamo. and CMkanbw copying papara. Skwa 1*71. PCRl wara mW in ika Uahad Stataa only for UM In doaad lywarna. Iraarding la Aw Tank fcikAancw Contra! Aa of 1774, nAw inA k*AialaHi oara praanibMaA M Indl Am aMndkaMM aaA aw af PCRa TMa Aa aabablaA dm iM US. AMAntOaB of PCSa and lanuary I, IT, and tkw ad OS. aab and AMkmisn o( PCla and July I, IWf. Howaaar, aanaMwal aaanari PCRl wtd aaa* among aorkara wha Maknab mnaforman and capadtara, and among tha gwanlpaguhlbaaia contaminatad food. During ttw pan law yean, inarm b Mw Maaiih affaata aMong IndMduab anpoiad M PCIa Mm kaa* nhnulauA ky: (a) Ika Mndanqr for PCSa M accumabw b dMwa and cartalnarpn^M (h| Dm nobility af PCRl and than par Aalanca In ika anvlronniana.-*,J and fc) dw dawanau-nad fengMrw Wide affeai,laafuAfeggwriam*a and othar Maw dhmm, b anpaaad laharaMry anbwla.r" Muck af Ada baaraat ana aapranad aa ika Natbnal Ckaferonca on PalychbrinataA RIpkMyla b Naaaah*. 1ST],1* and Aw waiilty af PCRl Hm kaM aaaanahalr nn laaad In tha NIOSH Oliarla DaaumiM on PCRk1* In Mmpariaon to 1M AfSlshW * Im4f--inH HrM* HONS 006527 tha aceumulatrd information an acuta tone tffeett in humans and atom effects in animals, little ii known about tha chronic tffecti from lanf-umi rxpotun in nun. Ta determine whether pate oceopulonil aapaaura to camiuarclilty praduud PCka hep caused any leng-tatm health affects, NtOSH MdataO an epldamlolcpk itady amanf weaken in Baa capacitor manefacturini plants. In conjunction ariih dila study, detallsd InOuavtci hygiene surveys atara aha conducted hy NtOJM an document tha levels af aapaaura to PCkl and other chaawiafc Dttcrlptb* af Ftcilllla lath ar the plants chosan far itudy manufacture afac* trial cspsdtansnd wars aaiactad bacauaa: (a) sach had a lac|0 arark tana; (k) ICk had keen ueed ter man than JO yr; (c) thaia ana cenaidanMe potential ter eapotura to PCkl atith lltda pattntlal hr tapaaura la alhar knaant teala cenaamlnanta; and (d) tha raaarda naraiaary la Man- ttfy Indhrldiiah la ka Included In tha ttudy aonulatlan arara readily amilabte. At tha time tha study was Initiated, bath plants arara (till using PCks. Plan! I H laaatad in Near York ute and ia divided inta two manutecturlng facilitlaa within claaa pmaimity, Om facilfty that haa waad PCBs tinea 194k piaduced small Induatrial capcrltais and tha other facMiy ha produced tarya PCMkad power capad- tart lima I9S1. Tha type of PC8a uaad hu varied dicing the yean how "Aiertor" (htanaanaa trade narna) 1254 (S4*chltrina) W1142 (42% cMarina) a 101k <41* chterka). In tddhlan, tavaral other klnda of oka wan uaad, but in a Mmltad numkaraf npaclMn. -- Plant 2. bread In Maartencm, beqn ta uao PCla to manuteatura capKitara in 19M. Thia plant aria chanpad the typo el POa uaad from "Arador" 1234 a 1242 a 101k. Until 1972, other typa of eapacltart arhich dM net contain PCka waantada at thia plant. Caatar aH wee uaad In lieu of PCia la produce tha larpa power capacitors at thia plane Both plana aaaamfcted small and larpa typa capaciton uainf tha lama panoral tschnieoet. The foUowinp briefly daitrikaa the taaatnkly process. Wlndlnp and art taanikly. The Innar contpananu af tha tanarkor ware wade of paper, tek, and tentatlnwe piqtlc film; around topathar; and tukeequamly laided Into maul caakiph TMa job wa dana In an ancteaaddutaftea roam whwe dtara arw minimal aapaaura to PCBa. Thsscfare, tha warkan kt thaw |ohi ware not ooneldtred **aapatadN whan chaaalnt tha sody aahart. Imprapnadaa Tha piwaaaiakted capacltan ware filled ar impreyiatad whhdiaPClh Whhlnthla era there ara potential ter anpoono to PClhind tharafata, thaw amployad In tkla aaaa waaa aonaldarad aa^taaad whan chmlng tha taady aahan. Final itutthly. Tha tapeoftha rapariton ware dated by crimping. nhbar ttappari. ar saldirlng, which htaahrad rorwa anpotura m PCBa. The ttporiton ware waahad to remove aacaaa Pgliky runrdm them through a datapant wath ar l dapfcaaar nich u tricMaroathylana. Finally, they ware rent through the final apwatlena Inaahrinp drying taathu, and painting. Them smplpysd In aavaral afthtu Jaka ware aonaldarad Hanpaeod>* whan cltoaelnp tha ttudy aahart. |VW.M(No.l1| Other area where there wee potential eapeaure w PCOt in tha ptama inahtdad tha takoranry and tha ao arhera rejected capacltan ware rakuki Appraaimatsly 1 OH of the taro arark faren ware wnptayed in teara arhere there had been potential upoeure PCfc Theta em ployed m three tobe arara comidwad "PCt aipaaad" ter purpose of cheating the study esho*. HhlorlcaPy, the work terra at Plant 1 hakaanranv- potad of tpproaimataly 50* whha melee tad 50H whiu femelet. Plant 2 ha had a lea hemapenenei work farce, with two-thlrdi beinp female, and raflaea the pewerd ethnic makeup af the area, which it larpaiy Coe Vwdaan tnd Porlupueie. MCTHOOS Marukty itady. A ritroapectlve cohort martallty ttudy ant cenductad la datermlna whether Indlvldutll aaaa PUtenaky aapotad to PCIt have eupariancad eny inerarae In cauwepaciflc mortality. The study cahartt wan datlnad mill warkan who accumulated el leeel 3 months of em ployment u any time in traa of the planet where there wet I potential ter eapouira to PCka. Thaw mnri iekt" ware palpated by the compenlee and vardladky tha labor uniona (at Ptem I), and by the NIMH ktduaolal hyptana turvayt ta repraianc tha hlph aapaaura lake. Tri chloroethylene (TCC) au uaad aa a deoraeer in hath plana. Therefore, If the work binary rerarq ktdteasap that an amaioyae had potential eapeaure ta TCf, the Individual am not Included In the cohort. This laituded very few arorkan. An eftert tea nude a determine the vial daeu (llvinp or dacaaaad) af each Inah Idud In tha cahana a af January 1,197k. Vital tuna wo deaenninad thrauph recordl mainainad by Federal and Scau aginrill, rnriud- inf tha Social Security Adalnlatralan, emu ntaur vehicla registration, and uata vital tutietica olTicae. Far those rnah vidualt who could not be located throu^ these seurraa, U S. Postal Mail Correction Saralcu and other follow up Marches were uiad. For all thou known take deceased, death cartiflcata ware raquaitad and cauaa af daaah ware intarpraud ky a oualifled neeatepitt accordktf u tha International ChaUflcatlaa af Dluaa (ICOA) in aflka at the time of death, and than converted to tfw 7dl kevnlon of tha ICOA. Those who had an unknown vital tutus wara aaaumad to baaMvu asof January t, 1979, therefore the true risk of mortality wu not saarantmasad. Those who dlaO altar January 1,1979, ware raaaidafsd to be alive for purpasa of analysis. Pcrtemycan wara accumuiaead ter each earfcer taartinp after 1940 when Imanthiaf ampteymant bseapaaad jake wara cempteud, and sndteg M die dau af daatk ar du study end dau (1/1/74)--whichever occurred fine. Using a modified life lahla computer propim shader M thq deecrlbad ky Cutter,1* she perms years ter eokeahurt atsra cansklnsd jnu 5-yr rslsndsr Muse poladl tnd 5^pr apt poups end muftipilsd ky tha carraapondbip US. whits mala (ter mala cohort manikin) and U3. wktatemate (for female aahart members) ran qnlfli merudey teara to yield tha eapeeved number af deathi. Penan leers wara additionally dlstrlkuead ky Syr appears ad S-rr latency (number af yean from dau flnt ampteyad ia tapaiad tat HONS 006528 TaMt 1.-VMI SMw f KS Wvrinrt Kmm i to aOw Kmv* M a* 4mm* Um>b>w MM TUI Nmwy--ff MtlM 530 51 sts 1415 n>Mi T*t*i MO 11 7 MS 5,115 44 71 15 *44 IIjOIO Mtln 411 31 14 475 Pkatl FWIUlM TMH M 43 24 *24 14,779 444 M 40 24*4$ OfMOTtcaf aj4 141 (3| 3447 19*11 joke) anifiriw. Obaarvad and anpaetad ami ipaeifU daatht wan compand and dMkrancaa wan taatad mini Me Patman dhtributlon. Induitrial hygiene mrwy. The detailed Induttrlal hyplane umyl Included panonal lima weighted air ai plat frui*ielectad)ahtitlae, Manila ana air tamplet. In koM piano, templet wan Man for PCM (Aroclor 101*), trkhloreethylene, lead, tin, ana rtnc. In addition, umaiaa tar tohiano, maMyl hokutyl katana (MIWC), ahtntinwRi, ana Iran wan tafean at Plant I. Thao surveys nan dalgned la dsaraeteria dm anpaauraa occurring at lha Mna a# tha survey ana may net rapreant exposures of privlaa yean, aperially Mean of Plant 1 whan exposura nap Nava Naan raducaa Nacauaaof naw production lechniaianracantly knitleua. MSULTS MartaNty study. A total of 3.M7 warkarl mat tha dafkiMan of Ma ttuay cohort. Takla 1 ghne a breakdown of lha vital status ttcmalnniont and the number of pmonyaara within each suk^ohort. Tha vital ttatua rrcartain- mant It Mil template. The poatlklllly Mat record! mi||it ba ashwng from die panennel Wat and to attamkla Ma Plana I aehart waa citad at the beginning oT the Mudy. In an afPsrt la datrr- mlna whaMer aligiMa warkan wan mating (torn Ma Plant I cohort, a validity Mack waa candanad ky Ma Naw York State Department af HaalM* adna method* alafp dmilar ta Mat datcrlkad ky Mank alal." Sacid Security Adminktratian (SSA) goanurly aarntnt statemano (SSA form 4l) from I943-1M5 ware aktaMad and compared to Ma namai anaaarlna on Ma admdlmid err. tannal racardt Mat ware uaad ta attamkla dn aakan. Tka ranlta of tkic camparitan yielded 15 addMaaal warkan (3.5% of token) not Included In tka Ptaal 1 wady ehen. TkiatmaW portion ef the papulatlan at rttk Mat kadidni front Ma itudy cokart Mould net nrlantp % Me mute. A Ilmilar validity chack waa not darn at Pkne 2, aa it appeared from our Impaatlen Mat Ma panannal file lyv tam had keen maintained kitaat Takla 2 Mow* Ma dlMrlkutlan of Ma cakartt by dura tion of employment In jaka whan PCI aapeane occurred. Tha dktributlon within Ma two piano la tana i Nat similar, with Ma exception of Ma female warkan in Plant I. when TOO L-OvwIm #r b4HvM anMa CaiMrt M>wn in PCS Imiiwi |0 FlMt Mtfa M (*F) 14 m lhr 14 yr Myr Mtyr 10 9T TM4 Ml 197 (334) M (15.11 99 (144) SI 1 til 149 (244) 47 ( 4*1) IIS MMM N tltPI 14 mm 4M1yr 14 yr 34 n M0 yr 10 W TMH 311 (314) 139 4144) 119 (17J) 44 j 94) 1i39 (U19n4) or iiimiim trMilMT. Fwnatai N <*F) 79 (394) SP UJ Si ills) 41 (104) 12 (314) __ J3 < 4.1) 50 FimIm N (RF) 397 (33.4) 141 (17.4) 175 (19*) 13 14) 111 (394) tit (t24) 93? Ttf n (of) 214 (224) 147 (154) 145 (19.1) 94 ( 9.7) 247 (354) ........&(`J' TaUl N (OF) 414 (24.1) 344 (144) 299 (144) ted i .ti 111 (19*4) T3H' ill AnMsar vf ImkwvmaiU Mruix HONS 006529 mtn im>lyi hid worked for 10 or man yr, tnOln Mh worki when chare WM a h%h frequency af chertam (M mamhi) rmployaaa. Whoa iho two cohorts art examined by yarn fleet cmpCuycd hi )aha whan PCi eipocura occurred, tho ftmalai In PVmI 2 vomm to havo hid in aarliar initial data of ccMMun, hi ftmt, 41.4ftof the maltiMd 45.1ft of thu famaho am ftm employed in PC* expoeura )aOa hafora 1*55. to Pftm J. 4.J of tha malt* an* . of iho imftmolM oara Iho employed In PCO upper* )o6 hafora TaMdl 3 MO 4 mmmarlia tha numOar of rfartha aOeerrad (aha.) ham Iho ecudy cohorts and tht namhar of dlhl llQim (tap.). Tha ill-quid mortality la loaiar Mao uipemd lo amh cohort, with an 5MR (SttnOardlaaO Marulky Kalla (SMR oheerved deathe/expected Oaatha X I00)| oftt (7) aha. a 70.7 ax*.) for Plane 1 and an SMR of 15 IN aha. n 105.01>.) far Plant 2. Thma SMRa may ha InfhiaataO hy tha "haatthy warhar aflhct.''1* Than la aa inaraM In ahaanmO mortality among tha total aohoit tar any of tho major cauaat of dtalh Recad in Tahla 3. TaMa 4 Mna tha ahtaraad and uRtetad namhar af Oaatht hy tpaalflc cancar cauta and for dirhaala of tha Ihtr. Whan hath aahartt era comhlnad, tha ahaanmd manhar of daathih mora than that aaparrad far cancar af tha tecum (4 aha. n 1.1tan#.) and haar canaar--ICBA 155, lSCA(}oha.<alJ7aan4.7haaniyiiaiMaadytl|iiHlcam effTaranoa (R<.03) htobaaraad mnm aaQaetad Oaatht acctarad in Mmalaa hom Plam 2 har cancar of tha tactual (] aha. aa 0J0 aa*,R < 45). P4r hadt aahana tonthittad, diara era 0 damha dna m Mnhidi of dm Hoar, hda SJOanraaapaatad. Phmaf thaaa aaaaa *a front tha flam 1 cohort, wMa ]J wara mpactad. Acarndhtg to haaphal raaarta, at loan ] of tha 0 paraana who dlad of chrhaala af tha Myar wara known,to ham tamuniad alrohal trodarly. Tha raladamhla hatwaan lalancy and tha mortality from a* eamar, aaaaaaaf tha lattmn, llyar canaw, and chrhpeh af tha Hear lathawn la Tahla 5. Far _a cancar" there h no aaaaram pattarn In aithar cohort. For cancar of tha 'm, thara la a tH|ht htcraaaa with an btaraam In tha latency period!. All of tha Oaatht Oua to Ihmr cancar accur before 20 yr of lalancy and thara it no trend of incraatlna risk with an increase in tha latency partod. Tha risk af mortality duo to cirrhosis of tha Hear does not thaw a contestant increase with an increase In the latency pertodK thara is hewtttr. a greater risk after a 20-yr period. Tha retatiovYihip between these same causes of daalh and lawfth af employment in PCRenpotura araaeef tha plants it (Iran in TaMa 4. Aa Indicated in tha TaMa, than is no increase In mortality with incraatlna lanytha ofep sura, except far cirrhosis of tha Hear; however, tha numbers in this comparison arc witch. IndtacrW hy^ana sway. Tht industrial hygiene turvey remits af ares and personal tempting for PCls (Arodor are summarited in Tables 7 and S. Because of differ ences in the production processes, the results by ipecific jobs or work area are not comparable between the two plants. However, relative comparisons can bo made, and tht range of concentrations observed in Plant I are lower chan those in Plant 2. In Plant 1, the time-weighted average (TWA) pwsoml air samples ranged from 24pgfm* a 393 jig/m*, md the TWA aroe air samples ranged from 3pg/m* to 476 pg/m*. The TWA personal air samplai in Plant 2 ranged from 170 pgfm*to 1260 pgfm*. and the TWA area air samples rangri from SO 44/m* to 610 pgfm*. Trichloroethylene was measured near the depreasers in both plants. Of II area air samples from Plant 1, ail were less than 3S ppm, eecept for two which mcccmcd 19S ppm and 321 ppm. At Plam 2, three area air samplei were taken which rangM from S3.4 ppm to 77J ppm. Area air samplai were measured for On, lead, and fine wear the toiderlng operations. Thara were no bundle levels for tin at eitbar plant Of four tampies cohered for lead and One as Plane I, lead waa deiered in one sample at a level of 12 ngfm* and One wm drtored on two sampiccai leveiiofland 24pg(m*. At Phm 2, ISsem* pics were collected far Iced and One; ah but one (41.2 pg/ Sin of the 15 tompho rmoalsd concentrations of One ranging from 24 to 94.1 pgfm*. Both personal and tree samples were taken in the wee imt.Nllta.IH m HONS 006530 MOMS 006531 of mmm opwnlom Nr rnminlm ilondnow md Iron it Plow I. Tin itmtmm amplM napM Ibow *M Wo to Ml n^m, aid dn km amplM iwpid Dorn 47 m/m* to tljpi/ni*. Twin pmanol im|Iii m mImM for Mom Min MIK during iilnllin apwidow w Wool 1. Tobwoo MnnniliMi><lliwiWmi))Mm<IHK nnpid from 1 to 5 (POL Aldnafi *oinpawno to Kfe w dn dww of tunny (Him 1 -April l*n, fkM MM 1977), own rWwhWv IKfMr In Hm 1, Uw MMwb ImoIi of ooponao iwy hm boon MoroopiiliilMM THoonp--wdiwuonrid 20 to 30 rrapoaomamrMmntofnadaiMdnlnidttaidin mUomI anew rMownitfwnnnf cohorw. Tin KB mlMum mM forlin ttnn Uino pwloni owo *relof 1234 and 1242, I'birmi Aioclar l(U4 wnflnt und in 1971. In iddMon, wwrol ddfnwil iiMHiw how bow idlid m iln fCfc (1* w Im bp oWd*) hm4 w Phot 1dim dn rty IPdOt. Tbm inrbidl Qonnlld ntrimp-- web m d^yowMo hwdkpbmil>i ii4 inoio MMlfi ilwl tyclolwniin dlonldi. It b not known ntdib Mbtoi bow boon und it PDM 2. DISCUSSION Tloro no Dw prartoui ipMoiiiloli^o ondlw dud bow odwnfend tfn IwiDMrm ImM Ntaaon bominoapo4 10 PCOk IndMdaoM patamd by riM ol handf WM inotid wl PCM (YuMo DImmi) hwn bww nodlod m dmlyyaanMtw dn bwldMMisobploio in Jnpon In IMS.*'* HowMr.tmrtModa nOi niim In hl^nr nmnWMmn ibid ami Nmd In no nwriMly piipond fCIb. A Md> winMw of ddn md op condWom wi mood In dn Yvriw pwDnw. In idddow itw ww% rilolwl md momory Undbip ibol Imbmd chinm In dn wlrroononiny of bwr wdi Mid i Omw--d luiiwnnwlun of biBroblo In dn nrwn of ibm indMduoD."** Eirlr npomroiadNip tfn Imldi Mina Dm Mow of dmo Mop bonbon rapomd w In racwn mdp of whamm wndnood bp dn Mon SWnl School of Modlclm.1* 224 mbmwbo worn (VH.MINo.lll HONS 006532 } 9 1 Kant. oamM UagMaf 0 Im-) yr Mr 1614 yr 11-10 yr > mm 11 0 Sa-I yr Mr 1614 yr 14-1 Ayr > mm 0 0 0 0 Suw-lyv WM 1614 yr 11-10 yr >Mm 0 0 0 Im-IM mm 1614 yr 1610 yr Mm 0 0 0 0 *O*A0avwA Aaaifa. i 1 Mill (t SMt 12J1 Iff 140 A.fO 611 00 S4 14S Ul 040 10..0. 60S A4S ... ... 0401 ... JO 444 040 60S ... ... 60S 0401 ... ... 1.70 JO 0.10 ... 613 610 ... ... 60S ... l*n M Uwn mn MU. mi hM. aea Wfai OtaMl o c SMt 1. AN Cancan (ICO 146204} 10 1670 100 2 4.10 4* S 2.20 1)2 1 1.04 M 0 044 ... II. Canaar f Raaoim (ICO *144) 1 0.40 200 0 0.11 2 040 issst 0 04} ... 1 041 111. UwrCMmrOCO * 144.140AI 2 0.44 444 0 611 0 040 ... 0 043 ... 0 043 0 SI IV. dWwaliAf OwUvar(ICOa401) 2 2JO 00 1 0.40 200 1 624 414 1 61S TOO 0 600 faMl 2 t SMt >41 74S )J0 US 674 too 41 91 no 60S 241 JO 40 nut 60S ... 49 674 400 610 600 ... ... 604 60S 444 74 607 114 JA 270 624 OS 610 HnyadalRMII M*aMMtMi.TliMMvn.alamsyiiimm mtari wi MranMla(tal mtf Mmh f Dm ctmnt nannMiyNam-TiMraaMalav jmafcnuof aknormai -- nPH^pm pi^w wrmmm vwwfwt a w^r fmrn tmmi M Kll mm fanntf m km lhr antyma ihanfM CMMa^C ^VM Am9 it B nMMat. --MIMnBniaB VMM-In aMtls afenannal nram iknaniic waiataak nMMhM (SCOT) Ml MM MndaMtf wWi iauM Imkaf fCfc. TtaMWMtnlMMy hlgpnMtoiM of Anal lull cmkKv MMn| I MkvM * 143 nnrkm HiavnlMMiynpart, IAi^ npnA mi Imtmm in MkM Am mMI(MM matamim 0 nto. (MM ntf.) and mmm *f ill. mmm amnni SI waaanti awHawl ibmim MMlayiM mt 41 fA^StA^^f OlOtO A^t^llOtfAAA At A Haw jArtoy pAArodMnikal taHhy* THh MMAhIi wi MoaN id Arador 1254 Owrifi| wHow pArio* OotvAon 190t And 1957, ofenf w*Oi ASpoturo to AthAr toaic And powitiAlly CArdnoiwik cowfwndi. In a MnwiavyMstoriw AmonQioproAlwiAjy SOOworfcAwiiiMloyAOiailMtioiiiirortwligofrei^* no inoKonont mHAnomti of pAMfAOtic caocaw wi AkAA^^^AO. HOAlAyAfj AMWOp tOA OAAAh fAWWAWAA Of 30 farnr workATA At tM WMirfiniirim facfltty, 7 caaaa of hlflf CAMAf WVV OtAAmt wtlATABA 3.7 CM WI tJtpACttO. Tin flnOlosi wi tnlflilMiy M< wi wot itjwH for AgA Of Mlfetl|i Thiw prorlowAtv npwH faAino of in IwaamA riik if imrnHir tH to mN|mai oikAooii ctooif of ihi pOMNN* Afl4 fang CMAOf AMOIIg WOflMfS AtpOAlO 10 fdl w not AwwHntAi In ifa pul Hoiy. Tlwo iro no OtAAMf flHklflO 10 Otf|MM WAfanOBIA Mf Ofay I itlArflf fWll from PAMfAOHO (AOCAf oMfa 1J9 AfA wpActtO. THata aro7oOAArwO OaaOii from roipiriory ISO HONS 006533 tyiien cmc, whareae 7J9 an uncut The only a primal cuteer In which the number of obaormd deetha an fMMr Dim enpetud an hr cmar of At Hewn ad cuteer of dulher and only a dyftlaeueaaa far hraaat OMt. Whan Mk eoharta and in |wp an combined, nonoof thooataacoe Mrtmoini|mcnMf < J5. Howoacr, the cncoea In Hoar tancar b noteearthy Ncmi II b tuntlutm wM the malnlapy liu ohtarred In Mor atory enimab expaaad tn PCba, itan effect! Nt bean noun In the Hver.*"* The tllpht Increire in deetha due I* drrhatlt of Mu beer In the Ham 2 cohort b alto oomntim with the notion that PCba hau a tonic effect on the Hear. In mo* occupational harith atudhe where cancer mortality It beinp teamed, latency If an important variable; Dm hypotheah kclni that than ta an inrroiiaC rhk of mortality once a certain time period liu dapead after Initial enponwo. In thta ttudy, thb hypotheah b dMIcult to enantlna peuina of the mall number of deetha. None of the eauue of death analy-ed according u latency dearly demomlraui thnacaociatlon. Rectal cancer thowc a iHpht Increau with an Inarouo In laaancy, and drrbecie of the INer thowt an Incroau in rblt with aa Innaua in latency after 20 yr. Then b no relatlanahlp hetman Inanoalni dwadaoe of employment in )ohc Involvlni PCS anpoaora and dte rblt of mortality duo io cancer or tlirhoah of dudtor. When cancer mortality b tturtlncd by Plwrt. it leer*, dent that mote of the tncaaaaa occur In Rant 2 toptcitdy among the female poup. Thb fhadlnp may be rdaudta mon expoturec to fChl at flam 2, ae Indlnacd hy the induttrbl hyplene reaulta. In addition, there wan an appu tunity for earlier enpoauntat Wane 2. patandady allowing for a lortfer latency period. Howorer, thb dbfuento In mortality may ho a funedau of iho tin of tho eahorta (Rami only No half Iho number of natron yearare Plant 2). and thue, limply ho a ttatbtlcd quirt. (Vac. Mine. HI lit HONS 006534 A MMMUI contogndfn* nriaMa Of knracsion variable In dab iMrfv It die eewtoto eflhct al atoahal in^Mlon on Aw abawvaf Intmw ( Wane 2) In mofadtr (row drAmIi Al Seer Hwmf( Afc cum be icinHy warned In On praam Hudy, linci cm anowNi Is known Am Aw bumleii of alcohol Miom the endro midy CONCLUSIONS eaeew teleiMy mull imaher ef dead* were obaweod, ihiloiw Ariwe Ihoea die fmAn el Aib study ace lawlaltve. AAomm AMttRty b tower dma onAoelod mA Aieie m m bmoaco to meniKty tor Ace motor came ef modi dm erne aeawlned. Among toe rwnar cmeeo. Amo one ImneMd cmv of die Heir Md cectwip Cbvfcodi ef dw Ihor wee die devoted in eeeafdWAlwaL The adglit eaoawea tor Hear emoor md (tortiedi ef dw Ihm are coatMam wMH eaodwdto lepeNed fledto^ow eapertowfitd ahmle aagmad to KOb d mmeM dm dwe may he waeaeebdasatalwmadHmawwaafdmdieiidoccu- ...................... AAA IQ SOI <U.Afetor 1134 md 1242). Hewevv, dae ftodtop tor dew ameer de cim reflect a itW 907 P99ltt^P4 It (Ot a^Ukt^kCte 0l4^rat Midi I mm Mm mvm rttoM m KM warkan im* Mpam mi raprirarfurthar im>i>nKir. Tlw aatoan mwM Rto to mpm totjj^ppjNtoitojHto^tta i2t Umw, to ftlcftartf Waawaltor; * atoms* at tot mm ato --wwWwffhiw mmtn liwlii,totmr imtliOn m# af NlOSHsPa toaoavy ato watotopatoto * fta fimtoiniOMa flttal * ........ ;to uiwlii t> * mmmrmmt latar m*m mm tor a m*r. m* Hmn totorttolaw invmt Vart Itm 9mnmmt * MwWi. Mr. Jama to mm iwKiylaaKtoar aitHaait m CtoiNtui Car*, Iwwiwii, Waal Vfcftoa, N1M ItoHM tor MiHw Mm J7, tor MllWIlH Apt M, 1MI. >wwi tor rurMM *M H itat m Oato f. tom, t.WJ.4, NIOSM, 4479 CalaiMIl totosr, Chiitotoil, ON 49234 MTIUNCtt 1. Itotitopr. 0,; Sato, I.: Ptoa. V. 1974. Vm to--Itrs af Ktl,*. MS. ClmlMto.OMk Tto CUmIhI IvM C& tom. 2. Tata, A. 4 1972. Lawfcaf aatotoartaaato Mtotay* to atoaaaa Mmn tf at paaral aaavltoaa af to mtoi, fa--aw flaato ItwprtaitotoI-- Mae 1) I: 794?. S. Prlto.H. A^ i4totot4L ttTXOammm to tato- lfa|wlwiwMln--Na.1)1:77t. * 4. to"--rt^totowM, AC^OM--dM^O--wieC. 1H. DOT tmi C* to martoa atonMi fmm ImNi mm Atom* 224:247.94 9. (Mnmf. 1973. Tlw PCS mry.^Mtol: I2M1. 4 Vi VMt Htoto, V. 4; Ompm. 1931 OtoratoM AtMto 4p }4t 41424 7. Mlllto, |. W. 1144. PXtoMjlt totoptto to--toiM to INHk Artohata# latoamwat Htait HONS 006535 i 1 rudunr, /. V.; KJUimi, K. UGarnto, H. M. 1974. Mychlarlnalad btph--yl biducud ittarmMn of biologic pan* matanMtfrat>rrbfAppfApmMC0/2B: 18949. . Kimbrough, ft, UMar, R. 4 GMw. T. B. 1972. MarpMagM chongm In Bvwa of fin fed pMycMorinatad Mphanyb. Arc* fin*** MmM 25: 35444. 19. Kimbrough, IL 04 LMv, ft. C.; turn, V.larmY**, K. W. 1973. AdtaaflBraab In tho m Pvor-whh partbtonca of polycMorHwttd btphonyb In aifpaaa Haua, Ate* Cmkon Abaft* 27: 39045. 11. Kimbrough, 9.D.,*nd Under, R. . 1974. Induction of idsnoflbroils and hopatom* of tha Ifwtr In BALB/cJ mka By polychlorinated Mphanyb (Arodor 1254). / Nad Concur Imt S3: 547-52. 12. Allan, J. ft.; Abrabamson, L.).; Norback, 0. H. 1973. Biological effect! af polychlorinated biphenyl* and trlphanyls on tha wbhomao prtmata. Environ Mm 5: 344-34. 13. Voa, J. C., and Notanboom-ftam, E. 1972. Compared* toxicity ctudy of 2,4,5,2', 4', S'-htxachioroblphtnyl and a polychlorlnatad biphenyl mixture In rabbits. Toxicol Appi Pfmrmacol 23:543-71. 1A Environmental Protection Agency. 1976. Proceeding! of the National Conferwwa on Polychlorlnatad Blphanyls, EPA 560/4 - 75 - 004. Waahiifon, 0. C: Office of Toxic 15. NIOSH, C0C, PMS, OHCW. 1977. Criteria for a recommended standard: Occupational exposure to polychlorinated biphenyls (PCS'i). PubUcatfcu No. 77 - 225. 16. Cutler, 5. J., and Edam, F. 1956. Maximum utilization of tha Ilfs table mediodi in analysing mrvival. j Chronic Ob 1:699-709. 17. Marsh,G.M.,and Entartlna, P. 6.1979. A method for verifying die coiapbteness of cohorts used In occupational mortality studba./ Oca# 4fd 21:665-70. It. McMkhaei, A. J.;Haynes, S. G.iTyrobr, H. A. 1977. Obsarmlons on tha evaluation of occupational mortality data./Occupied 17:126-31. 19. Kuratsune, M.; Manila, Y.;Nagayama.|. 1976. Someof tho recant findings concerning Yusho. In Aacecdbapi of aha National Conference on AbycAferfnefad Biphenyl EPA560/6-75404, pp. 14-29. W*ahtfton, 0. C.: US. Mm* mental Protection Agency, Office of Toxic liibunrm 20. Urabe, H. 1974. [Foreword, The fourth reports of tho body of "Yusho'' and PCS.) FvHuotm Aces bad (/ap) 65:1*4. 21. Hlrayama, C; Iriaa, T.; Yamamoto, T. 1969. Pina stmcaeral ehangm of tha liver In a patient with chlorobiphenyls Intoxi cation. FuAuoAt Acta bed \Jop) 60: 455-56. 22. Hlrayama,C.;Okumwra,M.; N^al,Masuda, Y. 1974. HypohHIrubln In patients with polychlorinated biphenyls poisoning, din Cham Acta 55: 97-100. 23. Meigs, j. W.; Albom, J. J.; iCartin, 8. L. 1954. Chloracne from an unusual exposure to Aroclor./Abd 1S4:1417-tt. 24. Schwartz, L. 1936. Dermatitis from synthetic resins and waxes. Am / Public Haalth 26: 51642. 25. Drinker, C. K.; Warren, M. P.; Bennett, G. A. 1937. The problem of possible systemic effects from certain chlorinated hydrocarbons./ ladHyg Toxicol 19: 21349. 26. Fischbein, A., Wolff, M. S.; Litis, ft.; Thornton, j.; Soilkoff, I.J. 1979. Clinical findings among PCimxpoaad rapsrltnr manufacturing workers. Ann N Y Acad Sci 320: 703-15. 27. Warbiaw, ft.; Fischbein, A.; Thornton,Millar. A.; Seilkoff, I. j. 1979. Decrease in vital capacity in PCBwxpoaad workers in a capacitor manufacturing facility. Atm N Y Acad Sd 320: 27744. 2B. Bahn, A. K.; ftoaanwaika, I.; Herrmann, N.; Grover, P.; StoHman, |.; O'Leary, K. 1976. Melanoma after exposure to PCe*s. N Enpl J Mad 295: 4S0. 29. Roush, G. September, 1976. Written communication to NIQ5H. 30. Taylor, Philip, ft. April, I960. (Personal Communication). N. Y.: New York State Depanmerit of Health. Does business stress cause high Mood pressure? Stress on thejab Is a real problem for most ofus. Many people think high-pressurejobs cause high blood pressure. Scientists and doctors aren't sure Ifstress causes high blood pressure. But one thing is forsure anybody, no matter how they reset to stress, can have high blood pressure. Ifyou have high blood pressure, youcan control It -with medication, weight control, less salt and whateverelse yourdoctor tdlsyou to do. every day. No matterwhat you do for a living.. keep on living High Mood pressure. Treat it and live. National rtgh Mood Prwura Education Program. National Haart. Lung, and 9ood Inaatuta. U S. Oaotrtmant ot Haatth art Human Servea* [Vi. 36 (No. 3)| HONS 006536 am in Mr rtcruprocamer pradurti. Ito UNIX syxmmo too--far itsporoNtoy** which panto km to emd tto Ml mp of eompoisn from ponoo- mam am tonpromd n tto trade pmi m a mmve by AT&T to lava tto system toco-- itandard a tto industry. Cowpsein ttot adopt tto UNIX systom ior their products pay licensing fees to ATAT totapt more yptiksM. Bell Labs and Western Electric have devel oped a broad range of software products based on the I'NIX system that the company will be free to sell after divesti ture. AT&T has already mode an aggressive move to capitalize on lightwave technol ogy developed at Bell Labs and Western. The company, for example, is optimistic about its hid in the competition for the contract to lay the first Atlantic cable using fiber optics technology. Bell Labs also is regarded as having put the compa ny in a strong position to exploit new developments in laser transmission of voice, data, and visual information sta lightwave technology and is rumored to to nearing the commercial application of the technology to computers and memo ries. AT&T is also regarded as capable of emerging full armed into the savagely competitive semiconductor industry. Western Electric is already among the d--i tog-- --mfoctorur at toagrm to canto. aM-gli to prwducii have ton --ii only foe too--! consume lion. HT* Ccrmnk appears to itpwu a view widely held in tto industry with hn appraisal that Western wiff to "a mqjor force in semiconductors in a couple of areas. Their design capability is very good and they've invested a lot of money in toots." particularly for semiconductor applications in semicustom products. Such products are based on standard chips whose design can to varied to suit customer specifications. Western will plunge into the vortex of semiconductor competition by vying for a share of the market for the 256K ran dom access memory chip, the prospec tive big seller among integrated circuits. This will pit Western against the tough est Japanese and American competition. Western is already shipping 296K chips for us own products, but observers say that it will have to succeed in increasing production and lowering costs in its unionized factories in order to establish itself as a front runner. Western is the developer of admired microprocessors used in its switching equipment and in fact is the source of many advances in computer science and design. Much speculation has centered on tto question of what strategy AT&T will he fodewmg in venturing into tto computer to--ess. Comp--y meat are eoncommtal atom tto raarar ttec WetoniwiN produce a panmto comput er and mute a toM chaffeagc to IBM on too--ground. For Be* Luba and its AT&T parent, divestiture obviously briops risks sod opportunities. Bed Labs offfcen jest wryly that since they managed the chaos of reorganization they should to aMe to survive mere competition. The reslruc tunng. in fact, is not yet complete. Ap peals about some details are slid pend ing. Furthermore. Bell Labs and AT&T will have to live with vestiges of regula tion. To satisfy the antitrust lawyers' aversion of cross subsidies, lor example. Bell Labs is required to deal at arms length in various ways with AT&T's marketing subsidiary. AT&T Information Services (ATTISi. so that competitors we not put at unfair advantage And other difficulties could arise. The move to cost-based pricing has upset the sys tem of subsidies designed to promote universal telephone service by keeping local telephone service inexpensive The cost of local service will me with divesti ture and a backlash is already budding m Congress. An attempt by Congress to revise the overall settlement is seen as highly possible. And tospne divestiture, tto stock of political --an union could still to transatinad along the network to Bed Labs, tomtom-- *> j " EPA, Utilities Grapple with PCB Problems PCB's in transformers may be a thing at the pem sooner then expected The Environmental Protection Agency (EPA) and a few utility companies seem reedy to accede to demands that steps to taken quickly to replace electrical equip ment containing potycMonnated bipton yls or PCB's. This appears to to a rever sal. at least on tto part of EPA. ofa tong standing view that PCB's in elscthcal --parent pose no sigaiftc-- berth hazard. Tto utility ctongenies. however, have responded as s result ofmeant PCB accidents end tto lawsuits that fallowed. In I9fe. when Coapest beamed tto industry successftdly argued before EPA that trsnsfor--rs MM with PCB's should only to replaced as tto equip ment--ream. At this r--.t--Mfor--n would to regloesd in 20 years. Tto cost to proceed any foster would be prohibi tive. tto industry contended. Now EPA is moving to dose tto looptoie. Because accidents involving tto retaoee of PCB's -- occurring much more frequently than previously be haved. EPA is roaiidtring a costly pro posal ttot would ton PCB transformers peresgtion that PCB's -- extremely tox ic. ftibhc concerns were hetghtened af ter transformer accidents in Baghmntoo. New York, and San Francisco re ctal buddings, coaling mifoooa of deters todeaai up. Other companies -- camge-- to calm public fears about PCB's. General Electric and Men--e. for example, have been active in dnseauaefiag inferambon dunum that the health effhetsof PCB's have been overblown. Although thought that problems with this perva sive sod toxic chemical were for tto most pert solved. But s loophole in the law allowed tto continued use of PCB's in electrical transformers and capacitors as insulation. A yew ago. the utility u months, t-- utility --op--as my they have decided to speed up tto reploct o-- prog-- not because they believe there are serious health hazards linked with PCB's but because they my they are weary of trying to counter tto public toxic at high doee levels, the compaam mam-- that tto dam on low-dose ef fects are fw less dear cut. Last May. tto Pecdk Gas and Electric Company decided to replace its toga transformers shortly after one of them SCIENCE. VOL. 122 HONS 006537 KrinrinkHMiDc i S Fraacaco. The body t r ntmm ni)r of ro iM Iky *om MW PCB n^ftemmi. "We ^ dradMhaMlIug Public perception." said compm* Tony Udwcll. Re cently. the Florida PWw and Light CoMpiR)fi which mvini half of Flan* da. took the sane step and will spend $13 millinn over the next 3 yean. Although it has not hod a major KB accident with its transformers, "we're getting ahead of the game before a problem occurs.'' said company spokeswoman Stacey Shaw, citing the accident m San Francisco and a similar one in Binghamton that oc curred in 1912. "The public's concerns about KB's have been severely exag gerated." she said. The cause for concern can be largely attributed to the fact tha. KB s are pervasive in the environment. According to EPA. there are 730 million pounds of KB's either in storage or in use in the United Slates. In a national health study. EPA found that almost everyone has a detectable amount of KB's in adipose tissue, although the number affected has dropped since Congress banned the pro duction of KB's in 1976. About I per cent of the U S. population in 1911 had more than 3 parts per million in their fatty tissue, a drop from 8 percent in 1977. The meaning of these low levels in not clear. But many studies show that heavy KB exposure is toxic, according to data presented at a recent meeting on KB's held at the National Institute for Envi ronmental Health Sciences at Research Triangle Park. North Carolina. KB's are in a class of compounds related to dibenzodioxins and dibenzoftirans. Ac cording to Ernest McConnell, chief of the chemical pathology branch at the National Institute of Environmental Health Sciences. KB's rank third be hind dioxins and furans when the most toxic isomer ofeach group is considered. Although General Electric has staled that "the question of whether KB's cause cancer in animals is unresolved.'' there is little, if any. doubt in the aca demic scientific community that KB's are animal carcmogma at high dose lev els. According to separate studies by Diane Norback. a palhelegiit at the Uni versity of Wisconsin Medical School, and Reams Kimbrough, a medical offfccr at the Ceaten for Disease Control. KB's cause liver turnon in rats whan tha animals are fed a heavy dose of I0B parts per million over a petiod of 2 yean. In animal studies, large doses of 70CT0W* tJ .minks Me dim of lab ct I with KB's showed a severe de keys exposed to KB's became Htfcrtiie. If. however, the monkeys were taken off the diet with KB's, their fertility re turned. It is not clear whether KB's are mutagenic. Several accidents with KB's have provided some clinical data, but Kim brough of CDC said at the institute meet ing that "it is difficult to sort out the toxicity" because some of the accidents occurring in other countries may involve different mixtures of KB isomers. An other problem is how to test for the wsemrhen inharpouphave rnmlmsd neurological damage with PCB exposure Mnongthe Taiwanese whocoasumud the oil. Other scientists also noted molecular changes in liver cells from patient* who have been exposed to KB's. It is urn clear, they sav. what these changes mean because the patients have nm as yet shown any clinical symptoms of dis ease. Arnold Schecter. professor of proven- live medicine at the State University of New York at Binghamton who has been studying the firefighters and others in- Wtwkrrs clean up af ter a PCB rmmtfaemerfire in Sam Fra*citco hut Mae. TV Pacifk Gat ami Eiectrm to ipemi JM presence of KB's and how to best de termine advene health effects. The con sensus seemed to he that fatty tissue provides the most sensitive sample far KB's. Some scsentisti advocated scrum samples, however, aa a speedier and less invasive test. The drawback is that se rum does am bind KB's as much as Several studies do reveal some toxicity of KB's, la IMS. about 1300 Japencse became ill after catiag rice ad cam lamiaaiad with KB's that had leaked from a hem exchange. With KB cancentratmaa exceeding 100 ppm. many developed cMoment, a dhffguring acnelike disorder. According to a literature search by Robert Miller, chief of the ipidsauplngy branch of the National Cancer institute, ame pregnant Japanese women who had eaten the rice od gave birth to chdfeua with various ^normak ties. Some of the babies showed dark pigmemnim, which djaappeared several aumlhs later. At team two children desloped oversown gams. The babies ed in the accident them, suggests KB's in transformers awy even he because farms an are subjected to the hem ofa fee. Soot taken from the from 27io I2gi parts par According to Mmtm HMpm. chief of the exposure evaluation division m EPA. fees nvotvmg tramfermers mid capao- ton contammg KB's are much more common than once than0*. "H's aa longer a one in a mdhon cimacc. It's much more prevalent. " By comactmg Ike departmeats, far example. EPa kna discovered that "there hove keen a com pie hundrad fees invoivmg tramfermevs. New the whole pictme ban chaagad.' Helper estimates thm there are 2MM to 30.0M traasfonmn with KB's, Whether otiwr utility compamas wR fek- low the lead of thorn in Cakfanan nM Florida ttuadaar. but Halpermeadmei thm the majority "wdl have la he femad to replace the oM eqaipmem." MQNS 006538 .iS2l fKMTPAMMMf OttmtUf CHtrriR Immune alterations t. FAITH w. MIMIMr r*R oaoaoiw uiA M l. LUSTER tmmmr * Iiwawm MmON Irtaom ftwwrt r^Mg* am, ac ;ni u ia , ^ M KO^WW' ly 10 iafeiioo or iuMor ct* ehahto*r. TIM panicatartr um tar ptaH*ta*MW* aioMwyK (PC>. pofrhrawiaoiai taphaoyta (FMk) ao* 3.},7,h-McMo4h taw 0 dtoMo iTCOOl. IHoth tm mlmmmtmmtmtm -- tar w--iririiy <F 2.).7,P>tirachtara4ikaMOtafO0 ITCOF), *Mt no taw art rqpona* for Effacu 'em pta aoi tauotagy of tyaphoitf m|IM an 41 (MIM wnh ihr Hor orpaawo. a io tatal ucttaHy a CMOtmoN MJ MtaimM ***"*. orpNwrt trtano proNarn C Ettmrr'SurtHlktfmtd iwmtataO Am /PPP HONS OOt>539 :u JC Vot. a Ftth 4. iM I Lmi and munphapa ii ii i mi im fanor <MAF). have profound effect* on ihe uvraohapc iwkiNm kdbn cedi are cyiota**: and h* a key role m the retecuoo o( ramorcetfcaadirMHplanu. AwrBhadhCMaadl*f. TWp ceth cedaboratr ft veto m antibody production agauut mow amipen*. Tiwpcmnr T cclh fun* moo 10 Moyrri rue activity of cedi (Taylor uf Batieo. I?*t or effector r cdh lAthenoo and Zemhale. Idt*l InaddMioa. lOere are uKfeCMiaut for ifte presence of I cafe tftai unam T ccth (Turk at., tftlftl. Voyrnwr and helper edit play a maior role m the repelcnoo of an MOrnuae retpoow. The fturta of FatontHjt hi bird* or ifte Porta romvkm ' numnah ipouiMy |ut airacwcd ly mphoid mwt or bone marrow) am aa a central lymphoM organ in *ftKh uaoi caftt are induced 10 become (Porta di>ed) B cedt(Fip. I I). Icettt ctr- ' > and temporarily rewde m ifte ibyrndt-mdependeat areat of ifte tphen (foHklet m d peripheral region of ifte white pulp* and lymph node* ifolftclu and pon mnpanic tumwlaiioo, B cad* tpaofk for (hat particular amipen proilieraie and develop into platme ceMt that tacreia antibody or tareo aa mamery vdK. The mam immenoglnbuliu lip) dam are IpC. IgA and IgM IpC ifte moat ahundani antibody and it primarily lymhemed dunog the larondiry reaponaa. It dMivte* readily huh ihe e*traaw,-ulor liuue uhare tomftati nurcwcganiimi and iheir loaun IgA it ihe mayor Ig in ihe tero-mncaua tacretion. and hi mat a to de fend ihe eaiernal torlam of ihe body Igftl it a bighmebtiilir weight antibody iftai i* a very eiiwieni aggtonnaior IgM it produced tarty ia the retpoo^ to iofectioo and it. therefore, the mow effective ftniline dafeuw. Thn divwon m ifte orgaminoo of ifte Humane tyttem darn not imply iftm T and B crlh are totally indapendent. For mom aupm. cooperanoo bttweep them h Mcettary for the generation ot an antibody rnpoan (the ta rnftail T ceB-dtpeodtm humoral mpaoitt. allhough ifte mechanum ot tbit cooperation not koown. touparanon by ibew T helper cdh it aot noceuary for all autigmm: type III pneumococcal polytatcftaridt and . end Upopofywccfcnridr are to-caUad thymw- imhpanihai aangani end can generate tuhtiannal amtbndy rrtpomra m nude, atbynuc mwe Dapendancy of T cell coaparandu aho vane* with the claw of im ................ H on T helper ceil thoo it the IpG (MM) (l.angrvaori et al. IW. Marcnphagii are nunnawly involved *o <lw M non pbme and ihe effector p In contract ie lymphocytet ik I Kagp. iPTftf Prttrmiinp of antigen by aval of n oof an It . d on tbs wtfaca. TMo mrfac bpand antign end pirhapt a tolublt factor from ibe mnerophoga imeram with lya ghocyte* 10 induce an immuna retpome. Immune afteiuiiou* Imeractmna of mocrophapn and wwunaed lymphocyte* ip the effanor e grubobly wedhtiad by ihoanrhar n Olffercm diranly - or indirectly - effect ihe tteucteeal and fuoouonol muoetywem. Therefore, in teihmtiogchemicaleffects onthem factor* tftouid he coowdeted |tw Voa. W>>. For eaomple. wbm aod penghrid lymphoid oraaot h found in a laauoty uudy o (here it aho a reduction io body wetghi. tpacml a " poawbduy ihm ibe atrophy groducod by o ' Gomaes. Idl4|. An iotcrocuno of ibe d aho be conudwad. unco vahoua hannanm I *(Wbita and Cikdndn. 1*121. I.J. P^rhtwtoaud blgbaoyh (FCSai The flrw tuggewioa that PCBt might offocl the immuno tywem imoh ganaiattoMoty ttwdm. lo l*hj Ftkk et al. reported ihm in imI tphnrn in chickam. Fodoninp ihm iniiiol report. Van and Ran regonad ihm ingttiian of PCBt iodwod atrophy of lymphmd theua i Sioulor rffecu on lymphoid iwue were aho abtan id ip tbo rabbit and Voa and Baama applM tit mp of tha them fCR pnpwairaoa. DP*. Ctaphan AtO aod Arorfar I2M. to tba dorth thin of rabbna S ta foe M day*, fcipaanra 10 thaw PCB pvapwaaiana rmnhad iniymghopan of ibe conn of the ihymua and a reduction In ibe anmbar ofpmmmol ca tphan aod lymph mdm. V and ran Dnel-Ciaminhau im lad i varyinp hrah (tmtpmg from 0 to IM mp/kg dletlofCTopbooAddind A for 4 or * week*. At level* aa tow IB mp/kg ip iPe font bah PCB pi ngntfteamty reduced ibe muoben of firndmlni h ' `` ` Tabh l.l). lo addnioo, ibere we* hgniOcaoi a weiphi al the Id mp/kg doeope level ime TaMt 1.21. A fun may affmt iimmameriup itinn wet fernnhad by Prhndand Tra d ihm duckhum M In* leveh of Aeoelar 12*4. n of louietty. worn .. . a pip* to CTopPan Add and 4 mp/hgdtacam " 1.1). RoawandTBiwanilf))te of Aroctar 1221.1242 or 1234 rwuhad m a rv HONS 0065*0 J C Vo*. M . FerrAWM /. Luster From an i. TCDO kutaaittt , halnpcumcd aromatic bydrmrarbnn Sever* ihyonu atrophy ha* been reported tooc cw m ahnow N laboratory emmale eipoterf 10 lethal or iwbieihal doaet of TCDO. Of cowrie, ihyuwc atrophy ootf m mduitoo of immuomupiMttioei wuce many r utmful moi y mm* cnynwc tetioni atmuupn not neentertfy io the urn* deptee a* TCOO. ttiwolotKaMy. the thymo* m TCDOrapnted aarmati > charatimrrd by dtpinion of lymphocyte* ihroupbout the corn* amt lymphucvit itaiimn hat baa* obtemd early after tspotmt |Voa et al., 197); Uepta et at . 147J; McConnell r at , 1970) The ihymn. medulla <t not affected at irrarety aa the cortex amt >n many retprets apprart mwilar to coriiume induced atrophy of the ihymut (rr> tewed by Bach. 1971). Intrrriungly. the ihynuc medulla ia populated **ih mature T ceHi while the carte* comaim pre thymic or immature T ceth (reviewed by Sprcafko and Anoneno, 1477). Peripheral lymphopenia hat beta ubaerved ta laboratory animat* following TCOO eiyawtc, although fairly hiph dmapn may be required iZinkl et al., 1971; Voat al.. 147)) Elevated rmmberi of emulating lymphocyte* have alio been reported to occur foMowinp TCDOetpoiure (Weutberfaud Zinkl. 197)) Ahttatiom in the number of circulating lymphocytes thould nui be cotmdered a criterion for tmoiune dysfunctioo unce suppressed cell modlaiad uomunny ha* been reported at rtpoiwe leveh that do not induce lym phopenia fVoi and Moore. |974|. The immunolopn effects following m vivo TCDO eapomre in both the adult and neouwal annual hate been wed charactertwd Cornea py tigadf to u hub at 40 np TCOO per Ip body weight ueekly for 4 weeks had deptmed delayed hypertemuivoy rem-noM ut iwhereuhw (Vo* al.. 197)). In adduron, the second ary. abhnuph not primary. mnhody retpoena to teiaaoi townd wat depretied a* higher thwagr In nuce. graft vt. how reantvey waa tupprnml following rtmapii of 0 ) np/kg body .mghi weekly for 4 week* (Vo* al.. 197)). wIMe l>mppoptohtnpiv* tr pooin toBaump utmulairo* wnh PMA were litwinf only at the 2S o/l| level <Vot and Marne. 1474). Sharma ei al. 0999) reported that a nutnhar ul mmeaiHuguef poranuteri were effocied to ence aod rabbis fodor mg eepovore to km In eh of TCOO (lew thao I 0 ad/kg/wprt for I woektl. Tbmio* chided dacraam m tymphapialifermive retpome to lygkgqit autnpmi fat leveh aa law at 0.1 eft kpI and dacreatet io antibody input littaoua tovoid). thin reac mny Huhantdin) and terum Moownoplohulin level* at dompe* of 1.0 */h| body Mt0ht fhataty fenhnp of tmoa vmh lavala aa ln aa 10 *f TCDCVkg reducod terum y ghibuhn. primary aod taeomhvy amihady men to S00C. ddayed typehypatw 'laactwm aod enhanced the urtcepiibilMy to Safwiundlli iofeciion (Munddl et al. 14001. A rccem report ha* dewrihed the uomune warm of 44 children l20hadcMoraroel h* ittidad * the immediaia area of the TCOO enwamiaanno io 4e*e*n. Italy I Heimam. I4?* Uwve nudiet found no abnormabtiet m terum iiiimaaopluhalin 249 concentrawom, circwlniioi level* of complamcm and lympbopmOferaitve remonme Of T and CO* lodb'emp OMOpea iimulmimi Itee aba Chapter tan. TCOO admnutitrwl during the pto/paaiumal or pomaoMl period no waamaf OornU few ham reporiad to came iMn (flam on ttm immaae tymrm to both ante mi ran and an ha a prwmam for TCDO-orianf mppwmiaoar laatt * iha rat Dmapt of J 0 ,p/kg m Mica mI rail oa vorioue 4m of piiwha aod wmomp mm prim vonety of ced mediand munane coerdama wdodtap ptabfmaitve teapoaan of phytohrmapphiiimn (PHA>- god coocaoavalin A (Can AhWMMdmad tphau. and ihyonc lymphocyte* (Vot and Moot*. 1474; faith aod Moon, 1977; Lower et af. >474C). delayed hyperteatu*My reactmot (Moare and faith. 1970; Fauh and Moore, 1477; Luun a y , 14)4*. Thoomi and VUaadill. 1474), yaft hou reactivity of ipMen ceHt I Vo* and Moare. 1474) and the aMHap to rejact tkm adofrafttiVo* and Moore. 1474). At would be eapaood. the affaett ore amre tevere when the chemical it adminitiered durint the pee- and poauiaiai penodt ihan if admmwtered udafy in pounatal lifelVoi and Moore. 1974; Fauh a if. 1970; Letter el af.. 1479c). Furthermore, the effeen arc ttbtiwly lanf laump. pertttttni up to 4 momhi of ape (Faith et al. 1470; Lower et al., 1479c). TCOO affect* humoral nunuwc nipomm but appaaeotly taputtw hi^wt dote* ttonad. TCOO e*pour ntm ftduetmo of totum y-plobulio leveh aad amihody retpome* totetaoua toiouf ut aduh guinea pmt (tuoailary dy||Voaet af.. 197)), rabbit, mice (Sharma et a)., (970) and pt^ue-fiordund caf (FFC) reapanam to SUITi in parinmady npamd mice iThaame and MiaadlB, 1479). Fetal and/or ' ' i by lotion whb T red n _ T (Fauh aod Moore. 1977; Lower al.. lT9cl. Tbmt w that TCPP induced mppmiioo of Teed fennioot wu talptnuo io* ftwtctioo u not affected IfaUb aod Moon. 1977). 9 irmafot of bourne y piebdin pti peaad mo/poatowDr to TCDO. but mot whacbcaoaad ihpprmiooof TceM o iagmif ............... .. )7k|. Lym- pboorobfuMitc ~pi------fodowu^ ulmoMioo wdb LR and antibody rmpooam tyoaoymoua tfoa and Michael. I97l Thippen et al. (I97S) tepanod tbpi lakrHalnl daam of TCDO mice 110 nf/kp/wook far 4 weekt) fodowari hy mfmiion wuh Miaonrdh barn rttuhed to mermsed monahty and dornaiM lime from nfenion w damb. haftettan by Mrrpao mm iFvrudaribimt did om effort monalby. It woo tobaadhopdy obaart tdihm mice treated wub unple or repeated do*et of TCDO rtvnbd a morkad lotriatr m tmp HONS 0065^^ :j2 JC N.IIFMiMMI LutMT wwwia of Eavtranmaaaal HnH Ss-mwcs. Inwt* Triaagh Park. NC 277**, US A.|. niail aomhar of pantone*! hukacytas (both tymonocytes and monocrtaal -at mood } Par* /Mowing inductm* Mk thtogtycoMaia a* nuc* potad 10 loa tavets of TCOO aduhs. WMt iha moftit of thts finding it prtsantly unknown. * N imartMtag to note that umiitr abtonatMis have bam rtfMriad following newmem Mk ryrinphntphnmiilc (Godeberg at al.. I9T1). AMhou*ft macrophage riiociiom do ooi appenr severely ahartd by TCOO. u is itHI coacttvabh iha tba uKrcttni taacipiibiliiy to mdotnaie may bt dw to a ><t unOrrnmined Tt DD indwccd macrophage defect involved dbai'tly m dctosilkanon. Atwmpt Hit batn mad* to ttatdMi tba otthanhiMi) rnpoostbi* for TCDOinduced utimuAotupprttsMt Whtla. to general, (ho* wudtaa have mi cvkaiaaiad in aafitMiv* findings, itsey have provided valuebh tnfocmauoo mho iba rataltoathtp between TC OO and iha immune sysiaoi. Early studies indtcaiad ibai iba atrophy of ihaihymus bv TCUOis not mdueetty mediated by ahered pituitary or adranal fontitoni urn* thymic atrophy occurs hi idirnahcmmiiad or hypophysectomurd rats traaiad mill FCDO (an Logtan i al.. IW|. Funbarmore, normal levels of drcuiatutg cortKoMttotds can bt found in iwmuwmapptnsad TCDO-iraaiad luitica psgs | Vos at al . 197 )l TCOO iraaiad an ha*t aho batn found io contain normal strum levels o< nnc (Vos n at . I97>. TCDO-induced ibymic atrophy is aos mused by riduccd food miakr (van Logtan n al. la preparation) or ahrialtone of serum fetoprotein (Vos and dockrsicut. unpubkshad dntal. Trammans of reposed akca amh thymosin, a thymic hormone which plays a >nnl rote in T cad maturation, dnea not restore normal thymte arckMaetura nor lympknprekfarativa rnpanae of thymocytes to T cad muoptna (Vos t at.. 1171). Tbs may bt mdtcah'ii that inmunompprestson is not due to a defect in T cek maturation. H was itpoind in an whir review that serum from pra/pmumtahy exposed rats wpprcsmd the w vitro lympkapralifrralive retpanies of normal rat tpfam cdf*. which would iadhma a cytoraate factor *m present m senna from aapmad atkaak (Faitb at al.. IMM. However. w lava Man unoMa >o toolira these finding) aaing saran froa pn/poataatady aapaaad iminunauppreaad aice (Lamar at d., oapokddhd kill. One of our laknmanas ham aaacnad fa sappmaor cad activity in pre/ppttnaady aapoted akca (Leaser at al.. I9M|. Thaa Madia warn proaptad by tacam findingi that a high mtidear of anaudnaupprestad cancer parums aad taaer baarap amaanis potaca a tab papulation a# cadi raiding in etrhar the B. T macrophage cad pepalninaicapph*e of producing akaHa factors wkied tappreia the immune system. Cocuhrvuon eaparumat as which ipian cadi from ooroMf aw* ware cabarid wkh sphaa cadi from TCDOirwad nw* which had wevtuntiy bam tramad anth mker anti-T cek aMtaara pirn comphdMni (todestroy T tadsiar mtiamycm C (to Mock ONA lymhasM but not produciien at wppramar faemrs) faded to tapprrti tymphoprohfcraetv* rasponaa of aoraal sphaa cadi ohm com pared to sphaa cads from simdarty iraohd normal oka* ILaltar at al.. IMM. Them stadws indtcmad that whit iha defective cad type raided io the T ceM papthiiaa. cad aokrdy a an espoaad pre/pndoataky to TCOO(Faitb i ike 291 of nadirs havemiratptid to study the dtrok tflbeh of TCOO an lp -t at *hto upowr*. In vitro ttadirt horn often Man hampered by thaw satubahty ofTCDO in phystotogseat buffers IMattumart and dm*hi, Wft Kama found that 100 ng of TCOO was only Jtk soiubh at l ad sokdioo coaMkang agoM voiumas of Amasfcytaidfoudt (OMSO) and phosphaMbuffmo* sdhn. akkauMiM dkiod of normal tcrum enhances tka toMhkty (Luaaar. unpubkshad okhrvoiinnak Monaihibu, Kouri t al. (I9MI showed tbm 0.1 ng of TCDO/mi at cokwo madkb wot Mtfficirm to induce aryl hydrocarbon bydrotyhh oitvay in human Ipw phocytr cukures *Mk Niwa <tal (l97]) raportad thm )2ta** of TCOO m madlk ia ioc to human lymphocytes, Vos andMoore<1974)wtrr unnhhto affeet the>ytm pkaprakferativc rnponw of sphra cads io T cad miingim m conaamraamm up to 2d */* csdtur* madia. Luster at i. <l979hi itpnrtad (hm Mhf lamimm* at what* iphatta wkh TCDO dkaohad in DMSO lid # TCDO/mil prtaa in cubam -------------PHA, Caa A and LI'S. Hnuavm. MogMh to bind to cad narfam nwwMiaffanadhyTCOOm ***** m amwmam n bmad^WTCOO. h M. hgMonbam mm^ u ia . dhcoM ih ohsanc* at a TCOO tempi** ia tympdornmn a i ihmltt hh|`HfT*CO"O#.a..*.P...*.a... ... , (Mama and Oh* K limy. A< dom M4H activoy (Kowi at aL. shat nf a mtmkar of concernrmMs of tba TCOO latapk. lino of Potaod at al. i!979t ibaatkamdk duding ibymoa atmpky) lavah. ThM may H0N3 006542 J C Vmt. HE. FmtkmmEM.I. Lmttr ii S I I ! f i i i ** 237 m9Al A water ot uten tew t mate. fwter a at. i I3T|) M PM w Oap tar M Oa** a 0 0.0ft )o 4.0 |/k| pr tey. Tte r 0 teh ite 4.0 a^/fcteaaga gnpaiwiMtitearcm ia ha l .0 op/fc* paiip Hr ifi itei iaAote aw teM^tete). Prhaary tateag :n "t 'V" *--r rnn> inilrtfi rtarttiiraifftite ' tail-- war--, i aaOI tapa of hPteci taptiiitaiteT 0aw>l>ao>--0aa wa ite te* pta of ite ataw. ate nOanoa a Iffratetei teaphatfia <a vanahtr ruta. iter* a w rffon m ite ttaap nO btate at Ik iter a MMMmiy m mterwli*. A aaNaaar rtpat ta ta itei adaaiwi oar occur m bah 0 ate T at fiaataa fatetat PM a ittei oft 3 a/h| fa 3 aaate ate 23 opA tar N ate Laakncki. 1*7*) li ha ton rapartaO iha Whte Lptera a fhtateaOr WPMhal Orpmte gtete baa ate ihyalr n ilptai litapr. l*M PM in ctte). Wteaa a al. | am (1*7 a*/k* Ote far I aotel ted ropte abate PFCt/ITcatea wta ate tea* aO tea. Afar 4 te a Iteg b aatw tea*aO ite aaaa igi tea* ibaa a a teateaa |WaPll tar 1 tet aa mm iffaii hr Pteaate l*7*|. Frater ate Am |l*7*l raparte iter PFC ropaaa a SMCa ia ate tab tai ninlala* I. >0ate fttate/bptar JOteja u aa Wta. Mb ate Hte. oa a# caarat teaaa. athopli aa rapaate teater te* Oatte PPCVMPaatb a aa*r aaa aUbaaP bp tea ai HONS 006543 i. *. Fau*a*4 \f / Luirr wnliHinl siudsn brpert aimed to non-human primates under lehorauw' comlmum i diwnw if there w a pnnm) for uMmamnepprestioa doses dveh ipptniuneiini thoit theoraicaRy detitnuud to Mom occurred m ih Muhipea paoeleiioa. The pnmaie itwdan by Aden and l.ambrevht iiotIi appear (videncf ado tuppnti that acme vt. cRromc ripcurr may induce differential effacit an the immune tysicm SpWnw weiphlt have been rcpmieddecreased fodowiap aruie cepesure H.usicr ei at. |07D; Widen ei al.. |0T* and increased after chrome npoture Kiupta and Moore, I0T|, Md may indicate recovery. While acute PM npoture may primarily effect humoral mediated smmtwuty. chrome ttpMiti id* peart 10 focut on cell mediated immumiy and in thtt wme, it noi unlike mute < low level chronic cyctophotphatmde npoture (reviewed by toed. 19731. Thd met be interpreted at indtcanna ihat PBBt preferentially affea tboaa cdh under(otoc** created proliferaiion since B ceth are narmally more proliferative than T ceth On iba other hand, low-level chrome npoture would affect T ccBt aa much if nor more than B celts because of 'hew dower renewal The severe PBB induced liver lettam that precede oheervmuai of immune dyifwacnon w rodemt may be more than coincidental. Since the primary metadolittn of PBB probably occurs at ihe level of Nver microemaal enrymet iBadth al.. I07>, quamuaiiv* and/or mtalhattve chanpn in PBB mctabolitm. may be reouwesi for immune luppmuon 10 occur, thd may rood directly through PBB or a metaboiue aennp on immunocompetem and/or precuram ceht fodowinp liver saturation or mduectly throupb aderanon of trtroid metahohem. indiemiag n PM- steroid interanion or amafoodm. la thd respect phenodmbnai, a typical md-rotontal inducer, it an umnunotuppreuive amaponiti whan amen in conjunction wuh some weak immunoktippteuive drups fSpreafico ft al.. l*74>. The various unmuae studies wnh PCBa and PBBt were aB carried out whit matures of which the mdkvMual campmmdt wil differ in their nmnunmnakny my in tlna respect the nod? of MrtManry al. IIP** d imereainp. Thaw the tnuehy of five haaacMarohipdanyl conpeoert in J.J.k.2\>.r-. 2.4.*.2\4\r-. 2.4.J.2,.4,.r-. 2.J.4.2 J .41- md - The tatter chmewel wm Memam mad and wmthnonky one to pro duce thyoma atrophy and edamo m tde chicken; toad mommas umdnr tn tdme found with TCDO At reported hy Putaad ei el- |lm. of a ranee of Ik hekemomid biphenyl conpemrt. only ibeneU.4.i .4 ieirnch>nrn . J.4.5.1'.4\S'< beembImn and M.M`,4'.3'-hewRtamm; which an ariadameee of TCDO). iaducad hepont aryl hydroaarhnn hydtmylma tawny Owe of d iM.j.j.a.j-f charmcad may ahat immune function- Them mdude d normal burmoot laved whmh mdomtly a duced funettond defeat of cet invoimd he tba in hormonal are known to affea immone fi defeat in lymphoid littuet could retuh h d cdh. defeat in cellular a ccd. Depduon of taipondlnp caM types as a rased of cRemM amp due to dirra lymphacytototicHy retuhinp m death of lympReryrn. I mmurational toduence of specific lymphnryse pepuim ` ' The likelihood it that mo chemically induced mmhdmrnn af immune n compdt process end in.olvei more than one of the den potential mm immune tuppression Abus. J I. and ImNccM. L iifIM R Ikntk. Toucol Aapt Pharmmnd. l. Id-1 ARhon. AC, Herumm. J.S. md Rfebrnb. M. del* af ubca an awcropRapes. I. Bey Mtd. IM, Ml-ISA Arhart--. C L. md Zmtili. M. ilQHt Mourner T cede me Md. Rd. )]. IR-I4I ` MM. 1C.. Ceteniime. M. md Mawand. C l IMP* MM Read Cham. 2). !*-!. Rnb, I f. 119793 Ct midn af ImanminpmeiiMia A*m> Na 21-01. Mam 1C.. HoRmd. I P. Aadmtno. M.A. I. end Rmroauky. C M. ttOSle Mycl . wmneml | ulmdtM.922-922 k I.M.R. livm fkma ddnWmMo af a iamptm tm *J.B n the rm. Cmtar Ran. M. >112-MU Am. vet. Mad. Amm. 147. Ut-Ra>. MOMS 006544 J C. Vo*. M.e. FookmttdM I. f --fr I 4*. A47 jwal Mm Wiw niwwir Towot. Art . (aMi, k M Nitin. I> W irtlJi iMwiaa M ml Mmrtw k ii4 m Hum, C I l*>ai MtOwai imiMMM iova to tte TCOO akm foi ji i*i - im I !* PttM 1*0 MMHM (MftMa. III tffM Ml tfB* Mtg MHl a* tto .atOaxa'cMi 'I'M* (m HM> Pm*. !J. 1*7 - Hi RiMttma. f |*T|| Iwiip h^mw o< tmh a lm l*h oI fin--ittt FF I Finnic m IM AAMA MtttMf. ItaHm. run. M)> I7t. Hum. I M ilINi r^vmwl latumaim, ZM EJ* . MartMl ScMttfk O'lOtll VruKan n ) . Fa>Ww. ( F and Gntiaa, 1E itwot Im**<* o4 NaniM ami I* *l*a ltO Aloma* V* Na t' Itoiaa. P . kiKtto. R I ami Ga*ra. P 1 tiVtoi NMWMMMm fbni of M.7> ifliiMMmaM**ara-r> M> m `it-------y aMa* T--woi. AM PtoaaM. 4). ))) toktottk. J i awl lutm. I I) i ivMi CtO-MuMaMO maaaa. * am W mtm Am* WMntMmMimiknuMi Iii<k4 AM *M*aaM *V II*-'27 Miwik, I I ml I iww. I It il*f*l PA I 4<al III H tmtmitO iMm* iH t)m**m>i* Apr* IlMMllI 4* AM . I A . kaat OR . P l . HaiMm. M.f HlM, It. Aa* u.. kMm. I A . tag* a. at* IMF. k. il*m VM M? **. ml Saapvt. V l. ||Ht i--m *>! hi-- om- * MM. <i H . Somhty. V M . Hattaw, Jft I 41. 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