Document NEmq9krxEjaVro0BjRLZov0vQ

(Folia Pharmacol, japon.) 73, 8B7~8?)f (1977) rc mi\v><D v /1- ^Rrntimt Win jj, ri/iili 11161, JbM> i'!-h illinS, rM:T- xmiiL'Amu'M-xw <aftl52l|:3fl23l|) SJ'-i 887 #*? o -A 500 (K.U-500, 5535 ffllUsRAStr PCD ii-ftB) 4H2 [ill. ISjHIi'il. 5 v mo i. io, loomgfkg wmw-cautt'iu, **, * #a^4i|'iLOTl5HI,1lltt4U KC-soo fcisaiNtt-'jCTI'ld'C *# anri:(b7(rjffi(kii. a-ic ioomB/kg iomg/kg instT-incr >k-n^d t o-AMiyffii-4,ik4iot-,t;. mu. jt-i >D-/-iiosu-rassiij; OMKrP. prnlulnrbital 101 OHWMU. KC-IOO H'JW]|!!|i|, I nig/kg KMBIC A o T 4 ttRflBl 0aioM>l/fc. (IF s a-/-A8flsii, SWMMKoiH'i-rsiB-TOjit* UW>ft,7> Witt.OiaMUiff glucose 6-pliosphausr._fflittffiTT*-ofi.-d-4>IO!ii|J'J! muiTOioii, BKt-mi-ociFMaxikfti Kc-soo H*a*-rciioai<ia:-o/o. a 'i'i'ii-.i/Ti5amiMaL.f;7 o moaotu. ***?m. tK-rm. wnwsitu unn(Mi>Wj;--*i. tt'ir.i?!'ioomg/kS bth. troinmitansMas-cAoi:. m I* pcn l'TIFOK)*ti!t6. KC-500 :!>4'l*ltT4i mails pob 5*>-, m Wll/jHI-m '}l,i2l 'll< a 4 S t, |0 KC-500 i|i!:Sl(lo I'CB /f *>ion, ir< >u-/-im*Kiiwnioi';(4'ai('f>ri'iifJn5iiE5>*;A>'sn, It rcii ft* i ri:ffl|!9(* twwt ict. owe* 5 i &'<!: Ma jtioijni.iim, mtx-?*=-* (pcb> jjfift4, Moiinitt'ju. -. 10 pen Id (dlJMCSttSIH >o-/-AB*iIBfWn4lt*i:0T. SMlyfoM*4Cf;'>. Ctt *>-e. v, MoiJi'-m, tuaftrarom' pcb ufasiiion-i-ifiiffliiHOftwc. {owaiitinsi'? PCB a'MWimi|-poCi4f;. JI4IO, PCB *-^>o^ !->-> 7 (-10 J: ***'>. -WlolliKaffl^Oll' PCB llf'l:l*H4%iilctf-rk'MlM-C'*5*'>. SHU PCB n fiA'lob, rtioicl-'i'-J-'.IS.AC'-I.h4 0 i 415. 416 PCB rtMi8ttMa4ia;R+4,3l!*Oc i 4ii l.fc. tof'tlflil. IFf *u-/-ABr,SOTW`:ai<. (*nIMttm'**B-*50O (KC-500) i-7, I-lomwiiTOMl/, trm'it)4fjai\ dl5HT-'}4'FitCT, 'J;lllxlCMiU!!E4lbf:fflTWa *6. * it a a 8D.JOI. **> , |. (rtiR80~IOOg, p*P7KJt.) 4BKI>, * ) - rillliOiTfWCl;* A 7 o *500 (KC-500, 5S*V #l*4fttf PCB Jiftt*), fi|ifllfc''?*l> 4 1, 10, lOOmg/kg (* (|*jR 100 g *fc 0 0.5ml (ji<t6HICJ fflfflfte, aio2M (MIliJiLTAWRiMilU). 1531,11, ^MWIV'/Vt niV'TJMlWI iWlUfc. mow 1 Ilf 101.1, *3-yht>4-'>U MISIBitfc. wfwiwiitr.aiiio i awxwi*. <1 iomiwj4'i'H:l -cisaa cmmiMtimaH) imu-ian* * (P531 ABoMUitK'l'ini 3 09 HONS 001148 AAR ft D1 li. II fi- a--- 7 71 KIM I- elite-, tti'WilKi'U'iif:. Knut>xa>jtmuuh'ioaij vj>z. **e ci*eo--rK.K.*. < *u **#-), -s l* 7/ l> T > M (lively,,1' '' "7 I 7 0 - 1 1.1 ( I- - 7 K.K. Klrtlrouic llrmnlotrit), Ihlllm (l.nnry i",1' v.l/jWi). '/>1- 0 - .7 lit (fi|. 77 -|i"t7j/ii.te}, n u o 7 u 71-;,t (Zurkowskin Oyjjll)), lliul'f-k Tv'T: (Rn|>- II*' (D/itJ;). 7' 71- 7j 1 ) ,7 7 r 7 - tr inl'i: (Kind-King" O/jiJ:), GOT, GPT ififl: (Heilman-Frank, 1*' tD/jU;), I.ruciix- n,,i>,io|,r|,,i,l:,-.r j,r7|; (Goldberg ami Rutrnbcrg" o')(/jlie). If *>/- A SMI. JUr-i P-450, Pl-O.r-A h, (Cyl. P.450, Cyl. Iis) ftMWffliii. t-1*, CFIC pcnlubarbilal 1C ,t -jlWilllCII-V/ilIl^ilW^ili l)'K8p'Clt*I C- fZ- N/NDl'H cytochrome c reductase /,rif|.U 0 FT', glucose b-plwspbntasc r/iflillljillkiiUt, Williams and Kami,,10' i/j'Wi, Klaasscn and 1`laa111 0)1}7J,lp. -r f 1 7' ftWDft. - *ttM<*>ii*in)iiiiiiffeii I'oieii i,'!>;jHiiciviD, aiino'/tmu Bragdon' Kttictt-sc. mist FOB tllUJlttfrCflCtf* >u7l->77( - (CC) Iti l&iaiiMW1' i tiltt-C J> -a. *wn#ttiuiKii:iiifcT. 9 7 za. ww-*fva., sk-w a x 4 o >**CS<-*GT#l/C. BBS* *l*ltl|inW'5 s hOMiiRIWjIlSiltfc Fig. 1 ICijitl:- KC.aOO re |, lOmg/kg MTMKtCIBU, llll mviiBCTWiy.iirfiaardis'di,'. -n ioomg/kg R-f}iirra. fi'}DBKUi4ian*r:')A'ij. 4iiiifltti.-)'- WMsn, mtR'di'H'itGTtWMWdWK'ft- Fig. 1. Average growth curve in rals Uealcd with KC-500 for 15 weeks. Fig. 2 ICii, peirtoharbilal KJt 4*M<WJICW.t* KC-f.00 COtUW4-7)1 LI;. HFillUInlil'IlflllitlTkl-a T*WWMBftW*>n. 1. 10. I00mg/kg ttJj|!llTtnflx2-J!HIII*'j70, 10, 20?olfi-S-.|iLf.-.. ft 'jfc'l'll'.'tii. 1. lOing/kg tt'iBITliMMWligt-iSG. 30aat?IJ;flK(i f(iS)^4-|i4<il> '-*! . 100mg/kg a'idfcuwKwasnimitMtcf set*<<t<. mi#*y?etfl*-nu-nTable I It K< 1-500 'i-larllfJKt'iUftlUft? ) h ttmi-J Wr. Talsh- 2 ir.Jl;j(, Table I ;:iln;,VT.it';-IT)i')iW/e -Jii-fH-TiLf;. KC-500 a'iic.t }<I '> Xltil. <MHK i'iiIiui tt-'M -1), -tfi, u'> ftT. lll 'RWiHVi. iliih'lllll'lhl ill? ? - otAMvilflA. ilitn'J y* :i ' Vi Oltll l:lt lluli'l bmine nniinupijnidare i/d't.CrlflJjirC',!--a li C 11 v >'R: ll`I t lOOing/kg |') ' t III T'111 ' XU). 10 uig/kg IVjlUT-litst'A-ICo.t P'u tf o ft.utBDt K-ti".* o> v),VC, I mg,kg ft') |!T C I tl > I'l I v) HONS 001U9 pen on u 8W> weeks Fig. 2. Pentobarbital induced sleeping time in rau treated with KG-500 for 15 vecks. Control rats at each point slept for 60 to 90 min. Table 1. Hematological findings of rats treated with KC-500 for 15 weeks. RBC*' WBC*' Hemoglobin*' Hematocrit*' Control 1 "'S/1'1! 10 n.g/kg 100 mg/kg 1003 166 1011189 882 1 24* 892187 U5*2 83 16 9223 79112 18.3+1.1 17.90.4 15.810.7* 15.1+0.8* 48.9 + 0.1 49.0 + 0.1 49.310.2 49.010.1 a} Red blood cell counts, x 10`/tnmJ, b) White blond cell counts, x IOl/mtnJ, c) g/dl, d) %, * |K0<(B. Each value represents the mean for 3 rats and S.D. Table 2. Organ weight uf nits treated with KC-500 for 15 weeks. Body* weight Liver*' Kidney*' Spleen*> Adrenal*' Thymus*' Testis*' Brain*' Control 1 mg/kg 10 nig/kg 100 mg/kg 545137 577166 506 1 29 423145* 22.413.0 1.73 0.32 0.70 10.03 21.8+3.3 1.8110.20 0.7910.16 25.212.2 1.63+0.03 0.85+0.10* 30.5+2.1* 1.5110.18 0.7810.18 293 252 25+1 23 2* 0.6310.09 1.660.08 2.03 10.07 0.6310.08 1.7410.19 2.0810.13 0.66+0.11 1.70 + 0.28 11.9810.01 0.44 + 0. (M* 1.6910.23 !1.91+0.09 a) g, b) mg. * p<0.05. Each value represents die mean for 3 rats and S.l). Table 3. Biochemical findings in scrum of rats treated with KC-500 for 15 weeks. Protein*' Glucose*' Control 1 mg/kg 10 n.g/kg 100 ing/kg 7. 7810.08 7.53.* 0.25 7.49+0.33 0.53 ' 0.33* 197119 194114 203121 1331.30 Cholc-*' sterol BUN*' ALP*' GOT1*' GPT* 123 + 24 29.917.5 34.4+13.9 74.815.8 36.22.6 123135 134128 231 + 29** 32.813.1 41.7+ 5.1 35.213,8 37.2+ 6.9 30.5 + 2.1 37.3+12.4 73.612.3 70.9+6.1 74.3.13.3 36.312.5 39.0+4.7 38.9+1.2 LAPf' 147 + 30 151 + 10 168 + 11 I97l 19 1 tt/dl, h) m.HHl ,,r ra nitrogen , mg/dl, c) Alkaline phiwpbntase, unit, d) Glutamic ox..dacetic transaminase, unit, e) Glutamic pyruvic transaminase, unit, 0 l.cucim; aininop.epliiLtsr, unit... p<0.05, ,<0.01. Each value represents the mean for 3 rats and S.l). MONS 001150 600 &m %n Tal>)o 4. Liver mifiosoinal parameter* of mts treated with KCoOO for 15 Control 1 my/ky H) mg/kg 100 mg/kg Protein*1 22.11 5.1 1-* 0.2 25.8 j 1.6 27.810.8 NAt >1*1 F iyt.b' c red. 55. 7.1 19.9 64.9.: 5.1 R3.4 + 4.2 135.(i 0.7* Cyi. 1M50*> Cyt. h,t Sleeping timet*' O-li- 0.flflj 0. 19 1.22 + 0.17 l.590.10* 1. 791.0.32* 0.46J.0.11 0.59^0.05 0.G4:' 0.05* 0. 75 -10.16* 71 51 + 7** 291 6**' 151.6**' 2521 f.2 214:'. 15 147 + 7* 832.14*' a) ntg.'g liver, b) nm/nig/min, c) nm/mg, d) pentobarbital (bOutg/kg, i.p.) in<)ucvi) slct-j) mi, e) ;4* funm d/mg/40 min. * p<^0.D5r-*-* pOO.OI, .** p<l).(>01. Each value repcesent* the mean for 3 rats and S.D. "' KC-500 tt'Jttl5j9H(C**U Table 4 low. CLVmc>t`UX rjr-t ffiCltt. Cyt. P-450, Cyl, b, ftfot(>V:\C NADPIl cytochrome c reductase jfiUtiJIj *VT .0(11 C r X A{il4> -u t'{l t. tZ pentobarbital 1C J: SIMUKH.'FfntA 6tMi glucose l}-pho*ph.i!;m- jrtttli, III lu. ' cixWi iro'/~iK)*xii-t KC-500 oiivnjsi. MifoBfTM. itii/,vutTffj imx tj i ng/kg BLk KC-500 ^7 He Stztf. ElWifcil'ihtT 15* <ft'>tKI tfi&3oafa> I0mg/kg , iomg/kg jaiiitficaotu. athzvmtm Cyi. P-450 *)t>tlfcic*fc'tttv u;i>sr, Fig. 3 lea 100mg/kg ttWfflUJl?*;*. Ir*iailttf#i-UXW mxtZ7y ***, m'MWbb't'tXo 1C. ^oy-Algan^i, !5i3TO'>bMfr,i bflH'fclbi LXxi'ji>lt *-- % drrrrjued Fig. 3. Klfrnt of KC-500 (at a dose level of lOOmyJkm on various pnamrirrs of rals treated with KC-500 (or 15 weeks (15 weeks), and of rats after 15 "tvfes of treatment folltmed by 15 week* of no treatment with KC-500 (30 weeks). HONS 0011*1 pch te.n ft. U 1J, Mi u'J -! <y(. P-150 .tV(,fy'at'U .N'AIJPII cytoihrume ( n (Iuli.im .Afl.f.i//., 'in; ; 11 y :: 1NIBII*< toltn U. pentobarbital i-.t 4Mtik!Wm'(!t Uti KS IR-P .*.->/; t'-Mi ;( hi-, ko-wo?, ntbj.iir,8H:-m m (tyi&fMia-* '-c& v -c > /; *:. kivoimmwit.it.p ('fiiljlt- 5). KCOIIO tt'jKi ijllllll'MUSl'.liHrtl' Pen iV'iA, Idfcl 2B0pinn oVi C.h >!:. Rl'T'III Vt, Ff!I. lfili(VN(i A uot: cc>V\. ifnMcA.ari'-v I a CTi'iH! W* a#lfc*i4i. * : n : IFB :S!r-.l: 7: 15 : 80K|(*4ii*.,y.-/ 4. A ; w, ft'ir'l'ilb t lS*Ulc'.f4i t.nOIHU 1 : 7: 30 : I50i<t'>. IfBtHKWtat? It* tomWii'i *4. s&k. i5an#ia'i' it* * tootsiijr.iA>Ti.t. *. K3-e!!,,; #, m;Kt`U5o~(io, in/iSiia-c:no~fi03s (i mB/kB iKT-at'.ji.i'KtA?,) i. f:, wirntw*!1 itiit isanict*vTuv'?nMi'.cia'-ct i: 10: ioon,|.i I ::JSitt44t. aojilHfllila*. nail I:: 36. linaTi.t I : : 20. Bil/imaTit I : if: n t /; <>, ym'f * aKwiKi'etiHu^tt'c Table 5. PCfl levels in lissurs of rah treated with KC-500 for 15 weeks (15 weeks) ami of rats after 15 weeks of licjstim-ul followed by 15 weeks of no treatment with KCi-V.JO (30 weeks). 1 mgl'iR 10 mg/kg 100mg/Vg 15 weeks Blood* > KUIllcyb, I.iver*> Liver micro* somrsr' Adifxwr tisurb1 0.12 (0.03) 0.51 (0.15) 3.71 (0.82) 0.75 (0.02) 4.47 (0.10) 21.4 (0.53) 1.87 (0.01) 8.33 (0,12) 49.1 (0.77) 0.54 IU3 (0.22) (0.02) 2.23 38.9 (0.47) (0.06) 10.3 282 (2.4-1) (0.45) 30 weeks Ulood*> KidnrybI Lm-rh* Liver micro*omrsr) Adipose tissue** 0.02 (0.01) 0.17 (0.05) 0.72 (0.21) 0.14--- 1.14 (0.01) (0.02) 1.14 5.04 (0.03) (0.11) 5.10 23.5 (0.12) (0.37) . 0.0? (0.02) 0.64 (0.18) 3.05 (0.58) 1.45 (0.01) 24.0 (0.04) 105 (0. Hi) a) /tg PCIt per ml of blood, Is) //g PC11 per g of tissue, c) ng PCI! per g of liter. Figures in pnreutltrses intlieate pg PCIt per mg of total lipid. Lipid contents in tissues of control rats were: blood (tng/ml), 3.520.35; kidney (nsg/g), 40.9 + 4.1; liver (mg/gj, 53.0 + 8.3; liver inirrnsomes (/'g/mg protein), 254 + 21; and adipose tissue, (nsg/g), 572+105, respectively. Each value represents the mean for 3--4 rats. Table full*., rirtlEliSiH I mg Aft Ij PCB l,t (/tg) 4.**>E-C*4- C C TUIA t>U 5 I|H WAft (iff) I'CII MMdlfK. na. HWjUlffi-CliUiAi'lidEW'ivii-f *', Jl: i 2 '/- a . Ja4l'lillF';3i:ij k'Tli, Wltrtl'(4t(!|^Uft. *ft,'KIAvr, H* kc 45, at|t pcb co .tj-tvWjl/tlAifK)Ti CilcKIt-f ICiidiLft. t<fis-e, IJlcS HHUiM's.-ltf* * Ub 4 7 t l-ry+J; peak 15 n) OtfEHMt/;. *C P, Fig. 4 tcR'+ldi |>vak l`t, Iti, 111 lltRJI&i'ijtlaft. 'iiJ, eO GC. /Jr'f |iilMarL/:iV)Wa:itil'T tMK'.fSiii'''l'i"j;-rvTi;'. ccmfUfi laT**v>li!ft*A^*aLft. HH>a Hid. (9<f. KC..5IXI, I ppm v (10 ::||:AW;! i*-nk in if- jj 4.100i UTMiH,Td,;j. isa a-owmax. iak ir.biit'ihH-mTwii-HiiiifiiaKftiHii, .*Kit;.m,F4fti>iki,'ri5an (xasn (.'llii: Wll I) r.1.13 < ll. 100 mg, kg PiV!f.:7sl',.lt{, peak 15 10 nig/kg FJ '1 Ilf * (1J; HtHuVii'l,lilliVi'ir)ii,!.i:'i>k'T,ii;rcF 4- KC-.5W ikOTillR+ifj i/ltu, nr,ai:|i L Cl'ft tiTC. :l!KirW:;'H'T*-t4. ISHfl. KC-500 ?!L-ft-7 hi'-ct'-rit. ir-WSlWillijlT.'kiei- l.ik iU:il4t;*f.ft, tt'/i.lfrlfl l cii:, .iHM&WkE.t.4i'it'l'W1'tll!4i|lliaf 4. e,iz. to, ......... kg ,J|#lt.h..T:Mriittt>MA: (Balloon tell |l|l)Kci') Jy 4l'lt)li A'l'^41 Bl 'lF|W.i-,i87, (tf: l mg.kg KK'jnT t'I.UIUK'llflHi!S',(IttCij;(t44(iT>.boft. *ft. 10, lovmSfltK I HONS 001152 ft HI Fig, 4. Do \ * % Gns-cliroiiiatORrapliie pattern of PCB in blood from rats treated withKC-500 for 15 weeks (15 weeks), and front rats after 15 weeks treatment followed by 15 weeks of no treatment with KC-500 (30 weeks). I'KWsasiMWKJftf;isaiiw.ot5hirmnna?Kift4t:i. t&iewist'iwvar&miisrui). *> f*.|t -W. 100 mufti Ki'iiitiii.t.oTU, ati5fflai-A.nf:s:)Kicaii.T. ifm Ill'll <) ai > X r >#IMlllM fr,ISf:- *am auv-awwTiawwatittKtti, aacMtsstKft MHainm) i*jaw 4,(If:. I5J3HO IOmg/kB Il'j|lflf)l:c, t.'r.pr <Tll CW'Pi'ft 4 (,. ,,n ____ _ l'J.k. />Mv./HC KC-r.00 n KC-'.no rt,j0ic2M. inaw tooing/tg B'iaiUA.Taaowwswwsn. ism-ii'iixTisaiaMau; >, 2) Kf:..-,00 I00mg,'ks 0!,tTK'>T{>i. aan-tt). Itin'i'l.lt tonwa'iBTiWHUWtfr*n. av*<M:iTisam<abf:-? n- 1 i ommma *j-< liut/if mn it'a**. an y*3-*j>M'U:n- * , ,,.. * r,|tffts U > < X^ntlis ftf:. 3) .kfflorflmclt'':. KC-:oo our: i "f(V. (V|x.ir ........... ::.t MlK5lfilit, I mgfti tt'>|B::*-.-CtKIW:nt'<(iSS'WSil(tt''l4-r. i f.-, i p',i:cu0lir; > o tt'lWitbTMSKilfl-?.'!. SWR`JAKM'TMMMi* 12''.ht-.i;-. loopMu/kc irji!tci.i*cjMWA'W(i.':. 4) waif wj fXi'W Ri:rt4>tSW!f:. MM' fl4l i b-CJnvrsi. *:WB: MB: *WiB9lfttl. 158 HONS 001153 PUB II cm :7: 15: iid c.I',ft'; i-M'il.U ciVil','UiABTSi i :7;30; isut<i. |||;, it:. .!:02> run :,U-,;mT*A. ifctt. Kife.ac?:unA. i>dtWitcS*!. Ilf; > / - a .1,41 tJ0?S|IW7aWit'Jt 'Sfi t <i 9. pub uho^K:j Oil BfcttMIGKfRiiiU'U-Cl'& i Uf;. 5) <;C /).y> a.I; peak if. i.t KC-siKi Mfc.H'UA'llWMi'-MtMa. U<4<Fi */-IdAi:i Hlt> ) wmilirf lfjicii. tttfiHfaxffi'I'l/Tt'fc. a'ifcH'iH.TiAtraifj.iT ii. Kill'.; HMircaMnifiiinre.i.<:.//. sA* gttwmottiij. tatffuu i>~s) r:Q iMMJFt'UIXIM* II < K < i l' ttt 4l'U PUD inM-raclio,. 4rT i11. o l)i Jd i - KUMO *J|K{ MB'!* 4 it' )*. ftafcnfcdOW&'KiJtvC, KC-500 * I Ml? i t t. at3^*511 vuisxatut' yjmannm-x.ti'4. MK'J AKTIIK* 4i, I'in..l.art,iul I;,t otlfjewiMili'ISU. B2ilMiTMi|'U'JWi:U:AH'ti:.!T- Alviftttt'4. lnJtJKftV.|!l.t. Ulrn and l>llB<ris> ICJt-T IBfiSUTl'4. C. i l j ()C A tj-b , IMw ku-mo !l(1l'7.'!:(*'<> / - > - WmttBliiittl'iC Ttt.'i&'l1 |V.U'CtU>M|t(l|f|V,IH';t iAVlW.'r (,-JC il.-./ai. tt'iMnt-XTisaifflHiau:? hsa-tu. *-*-![ iwiMg/k* *>ifiij!>,r!**)iaat4(anii*it>*->fc. ammu uimw riai Suniura iwmmum<> k i*tti>iiian'!i4r*ifl:rti>. 3, 5, 3', V WHJIt t'7 =. - * (TUB) tSM(T`20tl|Jl|MH U, (.|i|Jj TUB 1,(1. TUB *ftittl'|fcWI)TCB i,tMteT4t. JllatOrtl'IIHli' iCi U XI' -1. if; Banc 2SSO PUB M',iW4 HWppm MKNtf. BAJJfflv PCM iftiru.'M'.-VHA'X.T. MO>l< K iJ!,4t'!ittmil mW'i'itlWU/;(>',?!!';Uti>4. **. S'iii|>itl/T6)ti^S(rifa:iWn!#ia^/ilt *i*fiti. nilHiillic i i I'Jr1j JUII.'U11 OJ11 >~ 20 f-J rcB fJMrf4Ci*att'4. tMw'X*e>. (MS CfWItl/f; PUB Ut**ltIJItK< <. C0MS. MIU)K^T*(*it*4i&aui75C f.tii. KO..W# >/ i iiii. inn muttiy*i'crt<. ijvi'itu-tioawHiiiwMtK? ftit, If.fflIIIRVt CW.HIL/cUj*(tt30~0.W.Jof;. J*I'SiEHAf: |)U> Pub IIV; > O-/- A7(3 4?}*|Klfa;;.aM3Ti Ti>4t A*ii*U:. , PUB IIIFI y u-/-A.ftnna^*Kj; IHWI jn. 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Riochem. 44, 79 (1975) Abstract^ Tsutonm SIIIMADA, Yoshiki NUNOURA, Eiryo K1TANAKA, Sho/.o 1WAGAM1 and Yasuko MIZUTA (Osaka Prefeciural Institute of Public Health, Nakainichi, Higashinari-ku, Osaka 537, Japan). Recovery from toxicological nnd biochemical effects of rats intoxicated with polychlorinated biphenyls, Kolia pharmacol. jnpon. 73, 087 --894 (1977). KnnerhloroOU (KC-500, a polychlorinated biphenyl mixture containing 55% chlorine) was administered to rats at a dose level of ), 10 and 100 mg/kg, twice a week for 15 weeks. At 15 weeks, the rats were sacrificed to determine toxicological efTccti and to analyse polychlorinated biphenyl (PCB) residues in tissues. In otht-i groups, rats were sacrificed 15 week* after discontinuation of the treatment. During the administration period, the enhancing cllcct of liver microsomal drug-metabolizing etuymes by KC-500 was mure evident than the hemulologii al and serum biochemical alterations. Histopathology of the liver included degeneration of liver cells, single ceil necrosis, nnd lipofuscin accumulation in cytoplasma, and such was dose dependent. After cessation of the KC-500 trentment, several parameters reverted toward control values particularly in animals given lower doses. The order of the PCI) levels in tissues analyzed by gas-chromatography was adipose tissue liver./kirlnry^blood. Following a recovery period of 15 weeks the residue levels in adipose tissue ami liver were IO -- bU",, ami 30--ii0",, of those observed after 15 weeks treatment period to KG-501), rcsjrcctively. Further more, storage levels of PCI! in ndi|tosr tissue decreased more rapidly ibllovving discontinuation of ndiniiuMrntioil of the Imv dose levels ns compared lo those given the highest dose. From the findings in the gas-ehromatogr iplm analyses, it is likely that some iff the components are mclnlvnli/cd more rapidly than others vtlw-u the .otivity of liver mieiosomal drug-metabolizing enzymes is enhanced by KC-500 itself. M0NS 001155