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( II :i<! lr\i,vl Vof 16 ftp D li IVififiii-n 1'Hv> IV7H Pcrfitff) m Git*l Hn1*m OTICE: This sstsrlsl nay I e Droteotad b/ opjrlgbt TRANSFER OF POLYCHL ORINATFD BIPlItNYLS TO THF FOFTlJSt'S AND OFFSPRING OF MICL V Masi oa and K Kaoawa i)(i\uhi (piltyi of Pttarwticrvtictil Mintmn Ku I trLunLv .Vf A and S Tokloomi and M KiRATtUNr frtpittttHtw of Ptfhht livtiUb kwihti C-wurMiM //uyt^/u-k'u FkLuuLu A f' Jafmu \Ki`rct(frl 9 AtUfust IV77) Atafracl Mice wm frd nmihloi 500 fK( 500) a! a dicinry kvcl of 001 (conlroll 0<W K 4 oc H(> from lire day of imcmmaiipn <tirnl (Ijv IK of pregnancy and *ere ihrn killed rhe inmim" of polycMm in.fifti htpluii^K HTIIs) preieni m the whole bod) livtr and foetu&Cf of ihc mice were te<fCT|i\ilj 6 16 OS i and 0 1 0 2 ,, of I he toinl PCB intake regardless of ihe dictar) lesel of PC'li sIkimmu1 Ihal o lrKi'lacc'iMl irnnsfet of HCBs to foetuses occurs ui a relatively small degree Other pregnant mtte wen, fed * dert mnUining UOl oi 094 ppm KC 500 and maintained on Iht*. unlil ihcir ofK|>nti|. were S ik old I be ynung lone or io from earb lilled were killed tl weekly iiiHivak Ironr hirilj and rtn.il) ved liv ^CHs Tltc^c nffcpring contained ILK* <v jiiotc trmes as much PC H during laOdtMMi as was pfcscni in dir loctusc* 'nditating a eons/dcrahlc transfer of F*CB> m the milk ISSTKOIH CTlON Polyddciniuod hiphenvk (!*CIte) arc knoun lo hjw- iH'in l!tc cause of a mass outbreak of food poisoning calk'd Ynsho which occurred in western )nptn in I96K {Katstiki 1969, KuralMine Yoshimura Maisu/ak.i & Yani.ipnchi 1972] Foetuses from mmliHs with Yeslio showed some of ilie character istics of ilie iimease (Kiknchi Haslimioio Ho/umi Knpa Oroshi & Napakawa l9ft9, 7aKi llisanapa ft Antap.isi t%9r Scicial babies who had acquired I'C Us fiom tlxir nmlhris cithci Iraiisplaccnlally anil/iu tty bieasi fccdinp were also diagnosed as suf[I'Hlij: fiom Yusho (Yoslmniira 1974) Repioductnc deice is ban lx.cn riporied in animals piven PCUs (l).itilpii'ii I nulli A Carlson 1972, Lmdsi Gaines S; Kmihtiuiph 1974) and i| is evident that Pt'Hs plisenl in motlu rs ran alTcU Mini babies 7 lie study dtsijilml hex was utiderlakcn to obtain lurthei qujlii.iuu luul qii,iniii,nivc dam on ihs transfer of PC'Ms llimnpli ihe plrtccnlu and nidk of prepnant and Ian til mp mice r\l*t ttisn mai Aimirmb (ind insmiiNiiirniiou rthano! n hexane walrr sodium hydrnxulc anhyilmus sodium sulphate and silica pel weic pm dud for PCU analysis as de scrdxtl pievionsls (M.iMiiln Kapawa K. Ktiraistmc 19i4| K.mulilot S(Hi rttul K.nicihlo(-fi00 were pro'idrtl hs K.luipjftuIn ( lieituca! Industry Co Osaka I'CH is(,iii(Fs sun ptnshassd frmn Anal.tbs hit Ntltlhllasul USA or ssntlusiA-d in our laboraltsry 71k pus rbri-m.iioyi,ip|i usctl was ,i Shimadru OC-4HM with an iteeiion caplinc deticlor and a pl.iss iiihiini! (1 mm > ^ in) ri'iitnminp Clnomosoili W AW l)M( s |f-0 SO Ills sill Ui.ilsd ss n h V',, sr-io l In cohiiiiii u mpri atuis s\as 210 C and pure ntlropen |99 999",,) was usetl as die earner p.is ,u a flow rale or XI ml/nun Anlnnrfs rind diet Mali and female ddN nuu. werr supplied by die animal ctlilic or Kyushu IJimu u\ Tcsl diets were prepared by Ihorouphly misiiic ! kp batches of powdered feed (Oriental Ml wiib eihsl elhcr solutions conlaimnp Oil It oi MOmp Karecb'or-AOO and krasing the inuiurr lAponil ", the air overmpht to ciapnriile Ihe soliem flu mt lure was llu-n kneaded well with wadr and will, IIXJ y soluble starch frenpem piadcl dissolved m Itoi w ,ui to make a dough and pieces of the donph wui-luny 2 3g wctc pelleted and drud al {,0 C for 1^ In I lu driidpclltis calculated lo contain i> I U) c, HKlppm K,inrehlor-500 were analysed for PC Id h\ y.,-, chtomaiopiiipby (sec bi'low-) tin mean ImK i'ohuI from lripltc.Hr drtcimin.ttions bsmp (t()l 0 94 h 4 andfiCippm rrspccliu'ly L \pi`iinieuliil firiH aimr (email, mac wm diiidnl when 10 wk nld into font premps i)f 7 P ,nul in u,d insemination bet up conltrmcd h, ilu pi, sum i,( a vaElnnl plup Ihe piepiiuni nnci wrtt t ipul tndm dually and fed one of tin K.inuhltu 5CKJ cIu-k imnl day 18 ol prrpnancy when they were hillul lit, pit Iris in each cape wen weighed tveiy das an I (Inn consumption was calculated I oi rail, dam Iil In I uses liver and rcsl ol Ilu btxls apan limn i In iii,is me Iriicl were analvsal for PC'Us 1 wo nlliu ennipx one of iitnt and one of 12 mice weic mated mil i u ul Mm11,11 ly iind fed the pellets ronlaunni' 0 01 m 094 ppm PCHs fiom l he day of insumuii mn nnhl the cud of the ci|xrimcni Ytxlnp born on <1 n 20 oi 2t of pregnancy weic raised by thru <1 m |.i A wk one ot Iwo nflspitnp from e,tcli lun r King killed at weekly intcrsab from I wk .ifdi huth Im wttrvle-lHxIs I'tH analysis The tlams wue k Jk it n wk 5 a ltd in each east, the bur and llx hm ol On Ixxty apart Tium Ihe dipesitie tran wen nn.dssij ,.p ntaltls for PC Us 7i MOWS 207476 Y Masmia K Ka<>av.a S ,hkI M Ki kaIsi st TWf I M* up rum riilnilunn of f'( Ih "I ibr nho/r tWi luimngcnptc, lucr and fneiwsrv tif Jan,'. ftd kunrchbr 'IKI ll'ronqhtwl prigiuuui IP dm M level' tif TC U. No of in (red rppml daws/group Raul of calculation* Conen nf f'Clls (ppnil in Whole body l.i'er Foeur 001 (control! (im M Rfc 8 t: 8 7 Tola I tISSUC Fl 1 uia! tissue Fat 1 out titaue fat Total i issue Fat (.Ml 10 + 0012 027 + 0 H 011 + 0 14 n + f,o 5 1 4 11 l(KI + 31 (1 *9 990 l 310 0056 + 0025 I 4 1 027 II 059 23 + 91 2f> + 23 17 + 07 20(1 + Kg 'Villus arc minis + SD for continuations cipressed either as a iMopcunon of the whole Tissue or ol Ihe fat loniem An.iliiitnl iiieihnrfs 1 he odlci.it standard .mnklical method fiu 1'CHs established ht the Ministry of Hr,,III. irul Welf u e (K tin ashirii tlcda llcta ICashitntslti Kiiiinmr.t Kurjlsttni T.iisukJwa Tanahc Ici.i'hiin.i I upw iii>t Yiishinmra M.ismli A Mt/n;ani t`)72l was used fot the cvtiacliou separation and qimniil.t!tic lit rriisimmoll of POts Samples were first homogenized with 100 200 ml u-hrsanc and 20 g sodium sulphate m ,i W ,rrmg hlrndct The separated n> hexane soliilions wen- combined and evaporated to ilijiu'ss wilding r.ilit ti'sidun whuh were saponified with 1 i^NaOH in 50 UK) ml ethanol For liver sample s iht satxunficnlicin was made wilheiul esliaeiKm Die n-lieititie cxlr.iris of Ihe NaOII solution were eoiiiHiiio'* loneeniralcd and then chiomatrsj:iaphid on it column of silica gel (Wako gel S-l 2 g| cliitnl "till IMIml ri hexane The cluaic stas concern Irated anti silhiecleil to pas cinematography, the PC Us hong dtlcimmt'd by compannp the total peak heights of their pas chromatograms with those of a I 1 mixture of K anechlor-500 and Kancchlor-600 Kt-St 1 IN All tin picgnnnl tines fed diet lonlnimng 0 01 094, ti 4 hi 86 ppm PCBs gtew well llnonghout pregnancy, tin mean hoily weights of these four gtonps on day IK of pirpnaney iieuig 42 3 426 45 9 and 43 1 g, re sprctmly Their was no significant difference in both weight gam helween these gin ops The numbers ol loeinses in tills pi mg pioduecd by c.ith dam were uni mat (7 K) m cacti group and there weic no ahnnrmalilh's in appearance Tables I and 2 sumnian/c the results of the PCI) analyses of Ibr tissue samples from the fuiir gimips killed on day IR ol pregnanty The lesels of If Its accumulated in tht tissues of dams and (onuses and in ihe maternal livers increased wnh increasing PC H content of the diet [Tahk 1) The liter lcscts onts showed a rclaliscly small increase t x 2 2k howenr when ihe dietary concentration was raised from 0'M io 84 ppm Table 2 shows the total quantities of PC'Hs retimed in the tissues of dams and foetuses Ttiesc also incrrnsed when the PC H level of the diets was raised and the amounts ptrsem in ihe nhoh body, liver and foetuses accounted uspccincli (or 6-16. 0TK3 and Ol 02",, of the toial POH iniakt Thus a much smaller proportion was found m tin ftictiiscs than m (he other tissues However ihe pioporIrons did nol vary widely in the dilTcieni groups in spue of the marked differences in the l*CB Imls oT the different diets The PCH content of 1 5-wk-old offspring of dams given PCBs at a dietary level of 001 or 0 94 ppm is shown in Table 3 which also lists the total amounts of PC Us per Inter estimated fioni the nnmhei of ofl spring in the litter and tltetr PC It conccnh.num While both the conccnualion and i|n ltil.il .irimnni of PCBs present wctc always serv small in tin f<n tuses of the dams Ted PC'Bs thes were much larpn in the young killed during the lart.mon penod t.<boiu 2 wk after binh) 111 offspring weaned 2 or 3 wk .din hirllt Ihe PC LI concentlalion remained roughly ion slam rsen when they consumed llu did contaitune 0 94 ppm PCBs Consequently ihe nu.it amounts ol If. IK m llir bodies of offspring aged 3 4 k unrr.wd with time A dam piscn pellets com,nit mg ft 94 ppm T alitt 3 Mi-mi weurfcij nf I'CIli in K luilr-bi *11 hnmpgpnatr\ firm ami lot lir-n nf ./ijni.s fvij konnlilnr 'Ml ihroiuiKuui prrffitunn in dill IM l.nrls of PC Its in TccU (ppm) (Hit iionlioll oot b4 No of ri,ntV[OUP 8 12 H 7 Total intake ol I'd)/ tf'gt 10 i (M 9h + 7 0 KUO + OKI 9300 i MX' Tout wnghi (ngl of PCBs* >n Wholi tuxly Liver Foetusi i 04? + U 3h(42 0) s f + 1 9(4<| U( |S A) l)(KI 1 270(11 6j 014 + 0(Xi(I40J t t + 0 7 |7 2t 9 2 + 2 011 Of 77 4 16(0*1 0-05 + 007 (5 Oi 0 10 J 004 (o 1| 19+11 fO.'i It + P 9 (0 11 *\ llm t .ue means i Sl> lli. Iiglrns in pats nltiesis hung llu w ngtil of If U' lit ihe givrn tissue ii|iu sstii as a psr'i lit ' n (4 tin mini miakt _ HONS 207477 TaMc i Mrtin cant nitrations nml on uJ weight's cf PCBt in rhe offspring of Jgms fed Kanrchior-^tH) during oiul afnr pttgtutiu i | r'-c^ nf P( Its No uf 11 Etc'! ippM) i1+iTU\*pf<nni rco measurement ti i)i Hi n 11 n (t t*4 Total i ivsnp concn (ppm) Cont,n bitted on fm (ppm) Tola! wciptu |/<g) To) 4 I issue concn (ppm) Condi bused on lai (ppm) Tola! (#rg) Age iwk) 1 >006 + 0-001 012 + 006 0 21+ 001 0 96 02* 20 + 94 32 7 8 Mean values* for PCBs in offspring of different ages |2 3 [ * 00 K) 0006 01* + 007 0 59 X 0 ?9 on ooo5 f 0005 + tHK> 019 + 006 M i) n + O'v. 059+017 w. 0 <iS + n -f t I 022 15 34 65 + n 04 0 3' 2' + 11 72 2# 067 -* {) y\ 26 ` H k 4 y> \ alurs ui Ll i M) s 01)04 o 0 T1 * O dm ii O'l*o I tl> + 4 <L HONS 207478 fa I V. Y Mam da H Ka<ia*a S Triki l>rm> M MmatSIM show that the 2 4 5 1 4 .pcnia 2 4 4 2 4' 4 -heia .mil 2 3 4 2 4 5-livxaihlorobiphcnyls were the major tusil pound* ip the whole-body analyses of all lint, groups bid the last compound was Ihc mamtsoinci present in llir maternal liver Hb OIS4 IISSION f i Thetr ctperiiucnti showed thal, m mice t'tlls enter the foetuses through the placenta in relatively small amounts but arc transferred to the o(Ti|inne alter birth through (he milk in niuch larger quantimt Similar experimental results were nhscrvrd by othert in sludies on rais (C'urlcy Btnsi & Grim 1921 Mi.'iinoya Tintguchi Kusumolo Morrta Yamad.i llahn & Ogalii. 1974. lakagi Oiakc Kafaoka Murala Abnrada. Akaxaka. Ilasbrmoio lIda & Krimrrn I 19761 although precise compariton of these data it 1 not feasible because or differences in the strain of am mal used in (he dcpicc of chlorination or Ihe PC Us and in (he feeding conditions According to our ealeu lattons these studies tndtealed PC'H-tiansfcr ranot from dant lo Tot loses and to offspring of 001 0 2 and 10 20", respectively of the amount ingested Ihc corresponding figures from our expei rmcnis were 01-02 and 20 35,`i. respectively Thus Ihc figures show some leiel or agreement tti spite of the discie parretes ut experimental conditions The expcrimentnl conditions used hj Migunoya n nl (I974| were vet) similai lo ours m that PCBs were gticn (o ihc ani mals in the did fiom the day of insemination hill they used rats and Kanccliior-400 instead of mice ami Kancihlor-500 and found PCtl concentrations in tin foetuses and 2-vvk-old offspring to be 004 and 2 36 ppm respectively when a diet coni.lining 10 ppm Kancchlor-400 was given while the corresponding figures estimated from out experiment were 020 anil 10 pptn respectively fot a dietary level of 8 4 ppm PCHs (The value of 10ppm was obtained hy a rough extrapolation oT the figure obtained when 0 94 ppm PCHs was given) lhtts the contcntr.itions in mice were about five limes as pieat as those in sals but the difference may have been due ,u least partially to the dtsstmilartl) of Ihe two PCI) formulations Itnrson i. Mailai A Allen (19761 olil,lined some evi dence of transplacental and mammary movement of PCHs in monkeys The concent l at to ns of PCHs in various I issues of Ihc stillborn mr.Mil of a motikiv I ip I ("i.Ts chromatograms of kanechlnr StK 1A ( and of PC IK fiom (hr whole hnilv homogenate (Hi |Hr loci (C). n (nciiiv (IH and 3-wk-t'ld (i 1 iik) 5-wk old (t 1 offspring nf win Inf tS*Mppnv PCHs in the did troni ihe begin that had been fed a diet containing PCHs at a level as low s 5 ppm wuc much higher than those in 1 hi indents suggesting a fairly large species v anal ion tit the irnnsplaeenlal movement of l*( Its Thus dm ninp o( pregnant 1 beaks I 2 and 1 cinrcipoud ic 24S1.4 pent*- .'(')( S beta and 2.14.2 4 ,5' he**. cJHoiobiphenvi rrsjieiitsH) present findings may not be applicable to matt and there is at) urgent nrnl for qualitative and quantit.i ttve djta cm Ihe transfer and cacrciion or PCHs in nan uigcated a total of M/ oi 186 pg PCHs tin average dining 20 d.it>. of prrptt.iiiiy and I m 1 l of Inc- JilnmiIrvff/rnu ill I lid imcsirgaiion whs supported by taiinn Sinti the lol.i! PCD coiiltivl of (he Inter of grains from ihc Ministry of Health and Welfare * suili .1 dan) iiu r.i|vri 12 and O' pp .ti I and 2 wk Kvpciliu l\ .rfier hiilh [Table 31 the amount of PCHs ill 11 it I jml 2 wk-old offspring .tuuiiniid for a* hintM rs iniiili .is 22 and 3S',, of tin' nu.ii nilnli ol I be dam (nit ihioinaipgi.ims of t'CRs in the d.uns foetuses ami oflt|niiij; of min lid pellets containing 094 ppto PCHs .lit irpiodntrd in I ig I The peihs recorded iiaoclti i) A Mmli-r K J A .Sllcn I K [197(0 Rcprn diirioe clvstunelioii Ml rhesus tnoitkiv* exposed lo low levels of (Hit)ehlormated biphenyls lAroiloi I24t<| 1,1 ( risilh r 7 oiu u/ 14. 90 HONS 207*79