Document LKv6abgJwNeey744jpbne95nz

(Hi ftl, V-'i'T !V l>J- l i<1- I'f % ii;-* r.s .is. iWrr i ii.. i i't ,1,, It JJ Jr. vt n*: III... MM, rfKlh-HP ,ui>r rlli.ihul. l;f.O C*.1; of s* 1%: IIJ. ,Kii>i-s |lA, ri nl: tin' 'f NlnriMorv t'httfttinntt IijiI.iiimi) u>\`k irjr* t'hnntturot 2:1SJ- lie I'tTivTs of mj<>tM't'llt* Ahull.4* on ,`irHti ^fi<olr.v t` f.il/i.irt Vt. flip. 'Ih>r! A>r rortt.mii> S.\*. \'X4. fii* /nf>n^li4ih>ilc i Oljl.llUMlI. Citf *i oifAlfrf'injn>|it y*p 7 fi.y I27r.*^- KK, t! !: Atffrnr *lr. Atch Jm, fn Tfuv 17-4:1 -f-If* Irvtth .707, nW `IW. e| fit; J: nsilive ikW ("dim *lmi nml <J*' rinuj CAc/ri w'n*si e fis 'Lh^i^ic lt*i ' m flir. Anul liii ii |ro<ltK'|^o(l f\<l Miltlifl I :as, iu;o. itiIk.I of ilfi.f. >TM 1^/. noil ' I.'tiller It: Nms.iI ix.il rtiMMMixrniv. nixl MMott li. i- vys j<rn. Toxicity^ Chlorinated Hydrocarbons and Related Compounds A Itevicw Including (himinal.-d Pilieu/.mlinxiuM .....I Cblu< innteif Dihotiwifuinus iirnntf f), i\ itnhroiiiiti. At ii. (`itttntltlrr, < in Vxrlou* Chlorinated technical compounds, namely, 2,4,5UichlofOphcnot. 2.4,StnchlOrophon- Clilurarne , Ory.icclic acid (2,4,5*T), nnd Curopcan chlori nated biphenyl* (Phtnoclor 0P6 and Clophcn ACO), have been lound to be eonlrwmnalc-J with trace amount* ol chlorinated dibenrohirans or chlorinated il beniodionn*. Toxic 1*1 v/Neh pro. duces h/dropcficardium in chicken; ,n*o contain* 1 his disease is di'Sf'rilxal bv the formation of cornertones with or widiowt i viu and pustules. '] he follicular orifires are filled willi '.ehareous mid k<r,diuous malerial. Melanosis and a si-contlary inflamin iliiry chlorinated ilibunzodioiins. These and other tech r<-action may exist. Chloracne was df-scriliod nical chlorinated compounds Such as ic lech- for tUi first lime by llerxiH-ituer' in 'fiOO nleal penlacMorophc-nol have been imr-henied in who Ihtutjfhl it was produced by free chlo causing chloracne, liver disease, teratogenicity, rine. Waller5 in Ifllo and TiOciiy' in |!!i!7 x-disc.ne in callle, end chick odrm*. The liter*lute on the tonicity ol the chlorinated technical compound* it reviewed, II Is mentioned that J.4.S-T and (he chlorinated biphenyls also induce porphyria. Whether the vatioui disease entitle* *tc caused by the contaminants, combination* ot Hie chemical nnd its coniaminanl* or by the chemical* themselves need* Turlhcr evaluation. xujrRP.fled (he term "pernakr.mklieil." They felt Hint thin skin disr-r.se was produced l>y certain ehlorinaleil bydreearlions. .Jones and Alden1 were amoti': the first to report a ra. c of chlorneno in a 2li-i'ear-ol<l male Mrcrc niio worketl fur three years diwtillinic cMoritiatr.-d biphenyls. This patient also com plained uf ih.-situilc, lorts of appetite, and loss of libido, RlCC-KNTI.Y several chlorinated com- CWorneiw is one of the most frequent IxnthiU, site it ns lho paly-chlorinated biplie- forms of occupational dermatitis, nnd many nyl anti 2,4.o.(richtcropl icnox voce t ic arid cares have lieen reported in (he l.lniled (2,-J.h-T). have received a great ileal of at Sin!os as well as in Knrojie, pnriktdnrly . U-nlidiL rulyehlorinntril biphenyls (IfR) nerinany and Kiu>land. . are inereaM.(:ly found iit our environment Tricky-' reported in 11)19 that he personal mid 2,l.!vT has been used oxtensivoiy as ly hud t een sit least "laO to 2*0 woikers" in an hetbietdr. Occasionally these and oilier four different fnclorirs with clilorncne. Ho chlorinated technical comiKiuiids have caused stated lltal liver disease occurs independent eliseases (hat bear similarity to earh oilier. ly from chlorncne. and usually manifests Konte of ihese chemicals have Iteen found itself after an exposure time of four to six to be contaminated with chlorinntod diben- months, but may occur in as short a linn* as zofiirnns or chlorinated dibermodioxins. Tltc seven weeks. Occasionally loss of appetite, various diwases produced by one or more of nausea, and ulema of the face and hands the different technical compounds are dis are the first symptoms. Ahdonitnal pain atid cuss'd in this pajjer. Al trillion is focused on vomiting follow, and then jaundice develops. the various contaminants nnd their possible At nutopsy, acule yellow atrophy of Die relaijonsl'.iii to dilTercttt diseases in * variety liver is found. He cite-: Klimt and J.-irvik'* of species. The need for further well-coordi who reported cases of acute yellow atrophy nated epidemiological mid experimental ani with fatal 01111-01110 following exposure to mal itudies is pointed out. Hnlowaxcs, llnlnwaxts. which are chlorinat - Suimiiltnt for pubtienlion Oct ft, IJ7!; nrcepierl Mnrrh S. 10T., Krom Uie Ommltlr* Tuiiroloey Ijilxjr.t Ihrv, lvuvj. fotMiietilnl J'n>|htlii Art ih v, Ouuulile, On. Hr prill I rrpnenLi In Chiuuhte* 'l oximlaey ] Jitxu i- tmy. KnvirtMimeatnl 1'rolnlioit Aueuey. 4770 Dulonl lly, Uuur,liter. Cm 40111 (1 Jr. Kimbrough), ed Jtaphlhaloiios, ns well as the l'C'll CArocloru) were increar.iucly u.',cd alter 1990 to insulate cables. Teleky' cites many other case report: (Drink'' el at,T Jours.' Grienliurg et al,* Cotter,"' Mclechtchie and Itobcrl.on,11 and Coilier,;!). Von IX-ttin- Arth i'ncfron Health--Vot 25, Auf 1972 MONS 201553 'Ibis di-cnc in (lit- rabbit ear. (Tlic rahhit. car lest is ijiv-H ns a serreninj; lest to determine- whether a compound js likely to produce c hlor.ifnc. Olaf <>n `; in I oij donee was pulilef i him in,lif t) napt.i Tin' chemical, dissolved ill propylene idynil, is painted oij the i.ilitiil ear. If the test is positive, erythema occurs within two days and in a few weeks hyperkeratosis dc. vclnps.) The rnhhit skin offers as an experi mental tne! hoi I (hat wilt indicate the ability of Substances (o produce neneifurm derma litis in nnii.i' Pine 2,1,5-trichh>rn|ibcnnl rliil (av-.'* f.Vitllc wjd lifeline in v il.imia (nnti r,f poi onto; lion, diarrhea, pot and tb.thurgn fus couch, |>oor npf* matid.ii1 in Ihe bu liyjK.rkiralrr-is of not afTect the rahhit car, and neilher did sropic tx.i'uin.iO l,2,t,f)-(ctraelilorotx.iwcnc, ihe staninq ma shows central lob terial in the manufacture of 2,4,r.(rieliloro- celts with bile dt phenol. However, technical 2,4,.VI rich loro- linn of the gland phenol w-liich was used in ihc protlnclion ol bladder. Cystic 2,4,5-T did produce hyperkeratosis of (he (ithulc.s of die rer rabbit ear. It was concluded that by-prod ucts which had resulted during alkaline hy degree 01 fibrous , pancreas, was ali Chcnticil iUiieliite ot a cl'loiinjlrd <jibc-rirliOin drolysis of l,2,'l,r>-tctrachlorobcii/.eno were and a eliloUnsicd dd>cfuofuran. tlic causative audits, cro.is and cirrhcthc nephrons, an dtfcril'es the occurrence of chlmaenc in workers (xjsosocl to there chem icals. lie riles scventl references which indi cate dual dermatitis is (lie* result of die local efTitl or direct contact with (tto chemical, while (he toxic liepntitis results from nbsorj>I ion. Chlorucnc has l>eca rejiortcd in workers evj>o-ed to (-lilorcnaphthnk'tHtf, chlorcbi- Kiminijf and Schulz1'* isolated several con(.uuititmis and found that some of them, namely Ictraelilorotiilieiirofuran f Figure) at a concentration of 0.05% as well as U-trachlonxlilicnzodiojcin (Figure) at a conantralion of 0.00-)%, protluecd hyjierkeratosis in tlic rabbit ear. A hepatotoxic effect was also observed with these com)K>unds. They also found that pure (K-nlachlorophcnol did not produce hyperkeratosis of the rahhit cor, the cinlomct rima after ingiMion < chlorinated naj l-ink '* fed hc.xael swine and prodi. the liver and kid vaginal epiibctiv A depression of was also oS-cru Drinker and jtlienvl.s, chlarodiphcny loxidcs, certain pe Chlorucnc was observed in winkers of a liver of rats w troleum products, and solid chlorupheno's.H More recently Meips et nlis and llofinan biul McncBhini,'i reported 14 and 13 cares- of chloracnc, re.-txxlively, KxptiMirc to chlori West Gcruvin plant who produced tech nical pentarhloro(il;eiiol from hcxacliloroben/.ene.75 Tho technical material also in duced hyjjcrkeralosis in the rabbit ear. It is mats were fed naphthalene, pi hexa eh Inruriaphi ]>henyls. When nated biplienyls was established in most possible that technical pcnlachlomphenol of tliesc cases. Jlirimn/di.'un17 o'.Kcrved contains toxic impurities, particularly since eliloincnc in 15 employers wIk> had painter! pentachlorophcnol is produced by alkaline clllurou.iphllvilrr to moderate fa!' with cvntriloliu flat sections of glass with enamel and then baked it. The enamel had Aroclor fa PCUl incoi|>ora(ed }n it. I'Jcwig1* produced chtor* acnc esj>ciiineii(itlly on the wp|>cr back of hydrolysis from hexachlorolx-nzcne, Dibcnzod toxin and dibeuzofuran lhcmxolvc.s do not cause liver necrosis or hyperkeratosis when applied to tho rahhit car; however, they culls. Dc ;enerati tlic kidneys and (osis It can be cm eight mile adults hy apjd ying 1 In low-ox become highly toxic when they contain three that higfily chli 1014, jx-nlnchloroiinphtliak'ne, and Iwxachlo- or more chlorine atoms.70 Some of the work dure liver char ronaphthulcnc. ers with chloraciic also develop eye irrita cows, x-rtiscase Hauer et all* reported chforacne in work tion, hcpatotoxicity, intolerance to alcohol, drop in ihe vita ers' that handled technical 2,4,5-trichloro- neuromuscular symptoms, porj4iyri:t cuta the leading mar phenol. In some of these workers neuronitis- nea tarda, and psychologic alterations,-3 Ac is possible tha cubit wenknessr^jsycltotsathotofiieol changes, cording to nratm,01 chlorncuc wliw to re represent:; n blepharoconjunctivitis, and liver involve sult from direct contact with the chemicals incut alxo occurred. Kiminig and Scl.uli1' producing it. Crow,? on the other hand, foin.fl that pure 2,-1,3-trichlorophcnol din points out llint chloracuo can also be pronot produce hyi>erkcralosis when applied to duccd by systemic absorption. I liver dise.a-e. Sikes et af*= t produced in ee Arch Km-iittn llrnlih--Vo! 2IS, AtiR 1972 MONS 208554 - ^ 1` .'d'T a j.h.r.-lfW- r'v,v,1llir lest ,s i |,\i> d.l\s ,aln>is dc* ,-in j'i'fi lin' ability rm (lolii.ipliriinl 41 iiT irilhrr did nlim; tna> iiirlsloroit rivhlolOduel inil of is of (lit* I by.prtxlTabor by- rone wore vrrnl ronof Ihein, I'i/.'iirc) nl I .is letrnooiiivnl Mmiosis in fTtx ( wits nds. They lienol did rabbit ear. l;crs of a nxl techrxachliiro1 nl:o in ear. It is iioptipiiot irty since alkaline e. Diben* ves do not osis when ver, they tain lliroe the wotkye irritn- a alcohol. iia cutaoiis.?1 Acms to rechcinicn Is irr hand, o lie pjo- X-lllM'.lvC naplllh 1 lent Inn .,1 ^ ,1, , . i,..i, ,,IM .lfl,,j ucte t^rh aw"' 1 lii~ This di.-n'iiso in cWb was dexerilied l'y ItClS wt re um r'iiii^BhT''Iiiilk anil |irmlmi i| ()luf.-on;* id 10(7. A few years inter evi x-dbc.isc in the caT-i s ih trkn g_}hr milk. dence was pul dished showini! that highly They cited other autlit.r; who were ai.le lo ililorinaled naiilillulenes caused the dis- produce the disease wilh a complex wand eiiM*.-'' ('attic with .x-diis-asc show ft rapid preservritivr and a lubricant. dt'cline in vitamin A plasma levels. Symp HelP' tested the aliility nf various tomtoms of ixiisoninc include excessive Incrimn- pounds of the chlorinated lupbih.ilcnn lion, diarrhea, polyuria, marked salivation, group to produce x-disca.se. 1 fc discovered and discharge from Hie nostrils, A chronic that dichlorinalcd aud lr>cl>lntituili d nopli- conch, poor apix-lile, and numerous red lliatrnes did not produce tin- dironsr while maculae in the buccal mucosa develop, and te(rachloroiin|ilitliaieiic )iad an efltrl, and hyperkeratosis of the skin follows. Micro the higher chlorinated naphthalr lie, p, nta- scopic examination of autopsy material chioronaphlhalnut, hexaclilojonaphihnli-ne, shows central lobular degcneruiion of liver hcptachloroivaphlh.aleiio, and ocLichlori>ua|jli- cells with bile duct proliferation and dila* tlialcnc, caused severe disease. OcLncIiloro- lion of the glands in the wall of the gall naphthalene was less toxic Hum htxacliloro- bladder. Cystic dilation of the collecting naphthalene and hoptacidoronaplillvilciie. tubules of the renal cortex, with a moderate decree of fibrosis and degenerated cells in the pancreas, was .also olixcrvcd.1 In sheep, ne Chick Kdrnia crosis and cirrhosis of the liver, damage to Tn 1957,s<.3* a disea.se occurred in a large the nephrons, and winamous metaplasia of number of chickens which, at first glance, the endometrium were the principle findings seemed to represent on epidemic, II was after iupeslion of feed containing highly chlorinated naphthalenes.Huber ond Link1 fed hexacbloronaphthalencs to young swine and produced degenerative lesions of soon discovered that the residues of certain distilled animal fats produced the condition w-hen they were added lo the chicken dict,3s.ir n10 disease was called chick edema the liver mid kidneys nod hyiiorplasia of the beraufo it manifests itself with hydroperi vaginal epithelium with keratin formation. cardium ond ascites in chickens. Ducks and A depression of the vit-amin A plasma level turkeys experience ft reduction in growth. was also observed, Alien and I-nlich3' produced hydrojxiri- Drinker nml co-workors; found that iho enrdium nnd arches in chickens when liver of rats was afTectcd when the ani enough toxic fat was given lo kill most of mals were foci high dotes of lelradiloro- the birds in five weeks. ("Toxic fnt" is a naphthalene, pcntachloionapl'.thalcnc, and term used for fat found in chicken feed (hat hcxacldoronnphtliatcnc or chlorinated bi induces chick edema,) When the concentra phenyls. When Hchocltlc et nl11 fed hexo- tion of loxid fat was reduced and fed to the ehloronapiitiialcnc to rats, they observed mild chickens for 100 days, hydropercardium and to moderate fatly degeneration of the liver ascites dovclopcd less frequently, but testicu with cenlrilobul.ar vncuolation of hepatic lar hypoplnsin became apiwrcnt. Simpson cl cells. Degenera live changes were observed in aP* described prolifernlion and hygicrlrophy the kidneys and the skin showed hyperkera of tho vascular cndollidhun and possible tosis. necrosis of hepatic nnd bile duel tissue in It can be concluded from these reports chickens and turkeys. When monkeys (A/n- that highly chlorinated naphthalenes pro caca mu/tida) were fed toxic fat, alotxxia, duce liver changes in several species. In snbcutnncous edema, decreased total scrum cows, x-discasc of the skin, together with a protein (wilh a reversal in the albumin-glob drop in tho vitamin A plasma level, is one of ulin ratio), and reduced hctn-alopoicsis and the lending manifestations of the disease. It spermatogenesis dcvcIoi>ed. Caslric ulcers is possiblo that the vitamin A deficiency occurred in 66% of Lite annua la. Focal areas represents n manifestation of concomitant of necrosis and degeneration were observed liver disease. in tho liver; and the bite duct epithelium Sikes et nlK found that x disease could ho_ was found lo be nfTcctcd when it was exam produced in cattle wilh high1/ chlorinated ined under the electron microscope. Dilata- Arch Environ ltrailh--Voi 25, Aug 1072 WIHUMUIU iniuuuiH MONS 208555 / /- ChtoritM Crrf.vcn pftffllfum niftllKll (nOu1ir Kc. Al1 f.hlcx luphrnyil F*thUtcal n*4i*9% ** lh L)ir tMHh 0r*cl* an* L*)hrr(tw * ChlonoAteiJ nooMhAltrict Chtof.n^lcd brpoonyff Technical ?,4.5 r *nj Other chiQtophcnoti Cefisrv ireh/\4c*i 2.4,5-T from to^e lj| ro<ycMofin*iod biphenyl* X.DU** 1a CilH* HigMy eH'V'nA**'* n*plith*4ene* PHoietin* Tirocinia {IrcItmrAt ?,4.ri if* MmopHtild. pfulflc We r OptimalJ lfcJmr4 2.4.SI (ion of ll)o heart and hyjicrtrophy of the r:irefine uvisrtc wore also present.4* Toxic fat is not llic only product capable of producing the chick edema syndrome. Chlorinated biphenyl products. used ns n plaslici/cr in a paint, have caused hydro|)erfrardimn mid nseiles in chickens,41 and two of seven Uongalcsc finches fed l'CU dovrloiH'd hydroix-ricardinni.4* The seven finches of a total of 56 birds died during the course of llic experiment. A mixture of penInchloroivaplithaionc and licxachloronaphlha- lene, wIk-ii fed to thickrns, resulted in cluck edema.4* 'flic toxic fat which contained the cliiek edema factor was studied intensively. Click et al44 so|ximlcd a purified crystalline concenlralc which produced chick edema and decreased Ihc hate liability of injected eggs. Embryonic drformilics were also produced. Hick cl nl'* were not uhle io produce testic ular hypoplasia in cockerels when ihey fed low tlraa-.i of toxic fat (0.6% and 1.0%) to the cockeiels for 12 weeks, as lwid been rc|VKled by Allen and Ivilich.3 In 1967, Cantrell et lw reported Hint 1,2,3,V,fl,9-hexaehlorotliben7.o-p-diox in was one of Ihc toxic compounds producing chick edema. Toinitn et al41 had shown earlier that the healing of pcntncldoroplionol pro duced ocl a d ilorodif)eny.o-p-d ioxi n. HigginbolUain et al1* showed that ti-.e chick edema factor represented chlorinated dibenzo-p-di* oxiiis. The two |irinci|Ktl compounds iso lated were 2,3,7-lridilorodibcnzo-p-dioxin nnd 2,3,7,8,-tetmchlorodibenzo-p-dioxin. The nn I horn suggested, as a possible source of contamination, fata and fatty acids contain ing coinuiercinl chloroplwnols. When crude fats and (allows arc healed to produce fatty acids chlorophcuo) residues might be con verted to a cluck edema factor. It was mentioned earlier in this orticlo that Uic Aroctors can produce chick edema. The Aroclnrs (r*CB) arc used primarily ns dielectric fluids for cajxicitors anil trans formers, ns industrial fluids for hydraulic, for gas turbine and for vacuum puiii|is. and ns heat transfer fluids. They arc also used as plasticisers and ore widely distributed in the environment.4* Aroclor is a trade name un der which these compounds arc marketed in the United Slates. They can be found in synthetic resins, synthetic nnd nntural rub bers, cellulose resins, paint varnish, wax, asphalt, nnd in ullyl slurch, 'lhey kave been employed for dust prevention, moisture proofing, sealing, impregnation, nnd vapor suppression to prolong the residual life of insecticides. They increase the loxicily of dieldrin and DDT in insects.4* Depending on the 3mounl of chlorine they contain they arc assigned certain numlierg. Aroclor 1260 for instance, contains 60% chlorine, while Aroclor 12-12 has an opproximate chlorine content of <12%. Miller,41 in 19-M, tested a commercial chlorinated biphenyl will) 42% chlorine and observed liver damage in rab bits, guinea pigs nnd rats. Skin changes were observed in the animals who received subcutaneous injections nnd application of the material to the akin. The skin lesions produced by subcutaneous injection were histologically similar to those of cbloiacnc in man. Direct application to the skin pro duced inconsistent lesions compatible with low-grado irritation. Von Octliitgcn1-1'''-'-1 1"T' discusses some of the earlier work on (lie toxicity of (ho Arodors in his book The llalogcnalcd Hydrocarbons, Toxicity and Poltntiat Dangert. Nishizumi13 olxcrved changes in Ihc livers of mice and rr inkeys after feuding them chlorinated biphenyls. The aullror undertook this work because of in outbreak of poisoning that involved at Arc/i Environ Health--Vof 25, Aug 1972 Chl(V Cdam* Tone *al* i M/ilu'C of peni.Khloro- n.s pt >1 j r? *oM i*e nf.^vo- n*plOh.iiene least OOO people in ' ingested rice bran oi< inn ted with (More l'C'U i KnnccUnr tf> leaked into the ri<:i holes in a pi|L' used manufacturing proc mentation and at brown pigment dept born and new lorn Stillbirths were linn of the mother. Arlut orexia, fatigue, edr-n like discharge from and dark-broAiiish i Vos and Kocman Kieral polychlo<in: ens, quail and r.iL; the toxicity of tc Ixjlyclitorin.iled hip and Clophen AGO) which was produce The L`nroj>c.(ri con toxicity and produc er osis. Chick edem; with liuropean cm Aroclor I2C0. All duced porphyria. C three compounds bcnzofiiran. |icntnbrunch loronnphlha' the Kiuoihmii so nn from the Unilctl S carditmi occurred c Aroclor 12G(>, the a indicative of small lor in this prrpar.it Ter Iteccnlly, Bionci Dcthcodn. Md (un r.TWSCfVJl^MtWU At4M- IV HONS 208556 ypO*UfO nt* ir.n.iU'J irnvi piodud* edema, inrily a? ! trailsdr.udiC, ijvc, mid - used ns il ill llic iiiii* unkclcd in >mid in rnl mb it, was, ve tx'cn oislwrc I V.aiwr life of icity of H-mling in 11 icy ir 12C0 , while hlorinc sled n li ->2% ill fal> hamys :s'pivcd (ion of lesions n Wcie loracne in |iro> with 0)1 11)0 k The y and served rmkeys icuyls. use of ved at toTcchnlcxf Compound* Chftk [d*in* _____ TnTi'i.il* biohenv** Mulufr n* pcnUchtOfO' inti h^itichtororvjj'Mbiterit Table 2.--Toxic Conlantwvtnu n >d in Somfl 9Techo (ol Compoum ?,4,^lnch)orOpKcnoJ JTelrachluf o.!ij (rcinehtoroiJiJ>cr4 0*lft*trt *.o r (Telrachioroijifipn/oturnn TcIraeMorOihlK-iwnilitwrn Tovc t*t CufOpc.iA chlOrrnAtcil tM'hO'Hi (f*tcnocle>/ 01*0 and Oophfcn A CO) * Uilcd i<i TabJo |. J.2.3.7.B.9lt:aActilri'**>lMi/o p `JtOJto ?3,7 IncMlorOthSc**/'* p 'l*i**tr 2s3t7,Q Iciraclilo/oann'ri/r, ttos.n (rtlrlcliJo'OtlJicfi/iilkiMA f*crttooorotJ<Jcn#<>Cjr ah Hctach^nion.ipAfhAl'-n^ least G(X> people-in Western Jn|irm wlio had ingested rieo bran oil that bad been containiiiuted with chlonibiphenyls. n Japanese I't'H I Knncclilor -tOO). The eliloiobipbcuyls leaked into tbe rieo bran oil through pin holes in o pipe used for heat exchange in tbo manufacturing pn.vors. An increase in pigineiil/ition and abnormal grayish darkbrown pigment rfe)>osits in the skin of stilltxirn and newborn infanta was observed/"1 Stillbirths were unrelated to l'CH iwisoiiing of the mother. Adults sltowcd chlomcnc, an orexia, fatigue, eric DU of (lie eyelids, cheesclikc discharge from tlio -meibomian glands, anil dark-brownish pigmented nails.51 Vos mid Kochmi!55 sludierl llic toxicity of several ixilychlorinatcd biphenyls in chick' ctis, citinil and raU. 'J'he authors compared the toxicity of tivo Knropcnn connr.ereial polychlorinated biphenyls {l'hcnoelor Dl'6 and Clophen AGO) and one {Aroclor 12G0) which was produced in tlio United States. The h'.urojKan coni|x)iiml$ showed higher toxicity and produced ccntrilobidar liver ne crosis. Chick edenvt was a common finding with Kuroixvin cotntxmnds nml raro with Aroclor I2G0, All three compounds pro duced porphyria. Clicniicnl analysis of these (lirre cohijjouikIs revealed IctrachlorodiU'tu.c>furan, pentad llorodibcnxofurun, and liexachloroiiaplithalene as a contaminant in the Etirojwan samples btit not in the sample from Uic United Slates.** Since hydroperienrdium occurred occasionally in chicks fed Aroclor 12G0, the authors felt that this was indientiv* of small quantities of a toxic fac tor in thb preparation. by Emerson ct nl5' found a teratogenic effect of technical 2,4,5-T in rats. Apparently, the technical 2,1,5-T was contaminated with 27 ppm of 2,3.7,fl-li'lrachlijr(xlilx`nwr-/Mlioxin. In the study published hy Courtney et nl.5' it was staterl that the technical 2,-l.!-T which was found to he teratogenic in two strains of mice and ouc strain of rata was con taminated with 30 ppm 2,3,7,8-tclrachlorodilK-iuodioxin. Emerson ct nl'f tested 2,4,5T that only contained 1 p;wn 2,.1,7,8-letrnch!orodibcn/.o-p-d)oxin si comparable dosage levels and did not elicit a (eraIngenic effect. This finding was sidislaulintrcl by Sparschu et nl5* who studied teratogenic effect of 2,3,7,8dctrachtorodil>en/o p-dioxin in the rat. A slight effect was observed at a dose of O.lSVc/kg/day when the material was giv en by gnvngc from day 6 through day JO of gcclation. At the level of 0.5pg/ki,7<lny, the effect was quite pronounced Courtney and Moore"* were able to produce cleft palates and kidney malformations in three strains of mice with high doses (100 nig/kg subcuta neously daily from day G to 15 of preg nancy) of analytical grade 2,t,0,-T Hint contained less than 0.05 ppm 2,3,7,8-tclrachlorodibciixo-p-d ioxi n. Kcplingcr et al"1 rcporterl a decreased survival of pups in rat reproduction studies when fed 100 ppm of Aroclor I? l2 and 125-t. and poor hatchribility of eggs from chickens fed 10 or 100 ppm of Aroclor 12-t2 or 100 ppm of Arochlor 1254. II lias been said*5 that n purified crystalline concent rate from toxic fat led to the development of embryonic deformities in chickens. - l'eratocencsis Continent Hcmtlly, Bionclks Hcsearch Laboratory. In somo instanocs, (he saim chemical com Hclhcsda, Md (unpublished data), as cited pounds are responsible for the occurrence of ArcA nvira/i Health--Vol 25, Aug 1972 "oswrswww MONS 201557 I JO roi ay or tt\iii;ocM:noNH-~i<iMnnou chlornctic in people, livrr itixuiM* in several S|>ccicft, x-disenso in entile, rtiirk cifctiin, and terntohifiic or other c(Tecl nn the fetus. Not nil of I lie disease entities have tints fnr liecii produced l*>' nil of I lie cniintoiunls (Table 1). Some of (he romixuirids in question h.ivc lieen shown fo lie conlnminnlcd with cblori. nnteH dif>cii7.op-dioxiiis or chlorinated diIieirzofitr.ins i Table 2). The decree of eonlamination seems to vary with different coinixmmk. Some companies ninnufnciurnic these coni|>oiiJids have instituted clemi-up procedures which remove the greatest port of the contaminants. Improved I iyflic no nmotiR the workers ntul improved ventila tion of the working area have, in many instances, reduced lhe incidence of chlornene. Whether all disease entities described nrc caused by the chlorinated dibenzodrosins or the chlorinated dibcnz.ofurnns is not ycl known. Some of lheso chemicals aro highly toxic, as illuslmlcd by tlic fact that two application* of 10|ij of 21.1,C,V,.|rlmchlorodibetizo-p-dioxin n|iplied to luttunn skint1 produced chloracne-like symptoms. Single oral rinses of 20/,p to SOpg/kg/body weight resulted in fatal liver necrosis in rabbits.65 nierc is no readily available infonnation on the metabolism of tliesc compounds in nnimals and their breakdown in (ho environment.61 Il is probable tliat tliey arc stable. Crosby ct a)'14 found that 2.3,7,S-telrnchtorodibenzo-p-dioxin and its homolopites decomposed rapidly in alcohol solu tion under artificial light and natural light. However, photodecomposition was negligi ble in aqueous suspensions and on wet or dry soil. It is unknown whether the disease entities discussed arc the result of one or sev eral contaminants or tl>c combined effect of the chemical compound and its contaminant. Another unsolved problem is the observa tion (iiat some of these compounds such os technical 2A.5-T induce porphyria,*1 Hie chlorinated biphenyls also anise porphy rin.** Whether porphyria is the result of tlie chemicals themselves or of the con taminants, or both, is not known. Crow** suggests that the porphyria produced by technical 2,4,5-T may have been caused by contamination of tlw chemical with crude chlorobcnxcnrs, which wero used to produce the chlorophenols from which the 2,1,5-T was made, Hotter awareness of tho ixxaible cimtaiuriialion of lhe tecliniral chemicals wltli various highly toxic Mifmltiucm, welt coordinated cpjdcuiriilngient studies, rind ailditional cx|ierimeiiinl studies in nnimals nrc needed to clarify these problems. Clilorncnc has lieeri prodiursi r-x|irrinicn(ally in men by Shelley and Kligman fArch Dprni 7G:fiS9, 19.07). 'flic alillmrs cite addi tional references on cxlierinK-ntal dermal cx- lsurc of animals and nun to chluriailed naiihlhnlcncs. References 1. Herxbeimrr K: Uber Ctonkne. Munch Med H'rrhr 4G:278, 180!>. 2. Waiirr ft: Gcwrililicho Krtrankwiirn rltirrh prcMorto KoUm-vaiaeratolfr. Zht Gem Uyg 0:100, lots. 3. YrlcVy Ij Dio rcrnnkranklicit tOtwVnc). Klin ll'rchr G;84S-(UB: 897-rxit. Ipy7. 4. Jones JW, Alrlrn fl\V: An ri nrifrvm rirnnatrrgosia. Arch i)rnn Syph 33-1022.1034, IMJfi. 5. Tfifty f,: uts-r Nrmcru Vur-s-hunttsmcllmdrn unit Vorwhunern *ul drm Crliicl (In CJrnribrkrankhr<l. Klin Hie/ir 27:210.237. 10lit fi. VIinn VII. Jnvik NR Artion* of rcrtnin chlor* iiwN nrph: hnlcncs o( llw liver. I'roc Soc Exp Dial Med 35:118-120. 133ft. 7. Drinker CK, Warren MF, nenneit CA: The problem of poxaihla eyslemie edrrl* from certain chlorinated hydrocarbons. J Induitr Ifit Toxic 19:282 311. 1037. 8. Jours AT: The eitoloey ol aene with special retemire lo acne of accuiwlkmal origin. J Induxtr Hyn Toxic 23.200-311 1311. D. Giernburg I, Mayen Mil. Itoas Smith A: 'Ilia ayalemie ellert resulting from opoMin to retrain dtlortlulled hvdromrbun*. J tmluilr //vg Toxic 21:29-38, 1338 10. Cotter Iff: Praia, Mm inaled nn|tlitlialeneo in industry. JAMA 125:273.274. 1344. 11. Mrlerltlchie N(,F1. Kobcrlsnn D: Chlorinalrd naphthalene poisoning. Bril Mrd J 1:1,31-032. 1342. It Collier It: Poisoning by cldoiinaled naphtha lenes. Lancet 211:72 74. 1013. 13. Von Oeltingen WF: The Holotrncted Hydro- mioai, Toxicity and Potential Danger, publication 414. Public Jfeatlh Srrvire, 1965. 14. SthnarU L, Tulipan I, IHrmingham Dl: Of mpnlinnnl OUrtlfl of Ihr Skin, ed 3. I'hiladvlpliia, Lea and VeWw Publishers, 1957, pp 33G-.T45. 15. Men W.r, Albom J.l. Karlin HI.: Chloirrne from and iimnual exposure lo areclor. JAMA 154:1417.1418, 19rt. 10, Holmann MF. Mcnrcluni l.Tz A proaixnilo delle (ollicoloat da idroratbuH elorosoalitiiili (Amo ctorira). 0 flat Perm 103:427-460, 1352 17. Ilirmmeham 1U: Oreuiwlionni dcnnatalogy: Current prolilrms. Skin 3:38 42, 1312. 18. I'tevrig (V. V,ur K'meUk der ComcdonenbiUlung bel Chloracne rifaloaraxame). Arch Klin Exp Perm 238:228 241. 1070. 19. llaurr H, Srhulx Klf. Ppircrtlierg U: firm. Ilirhe Vrreiftuoeen bei tier Ifersletlieii; von Chlor, phenol-Vefblnilungtn. ArrA Gericrbrpalh Grruterbthyt 18:633-665.1001. 20. Klmmlf J, Schulr KH: nerulliclie Akite (So* Arch A'avirM Hculth--Vol 25, Aug HI72 (3,li,i.,hnr1 t Arlrrr. Per in* 21. Ail.ims ,c--l-nl |l,,r r 2 i 4. rit. 22. tUvIlr |H,n rfua li .'OiOa-yA, I 21. IS.r.in.l hi-.tilh ,im, 2.4.6.T (,l.-,nl 2t. tlr^un Klrhiiny -U-r 2*. t `roe | 1973. 20 ntst-va lie Cnrn-U 1 27, f I Anar lion and iri Ivmne hypr v,hr:tl rrtnrr 28 Sihes linn r,f hyp 29 llrork Chlnfin.,1r<l Arncr J Vet .1(1 Ifohcr <-|ttfin*i;r|4,i 4 ?.`.7-?V'. i 31. Srhr r VxprrimtnL nnd hamur 32. Sihrs mental |,n> route mlh prolut u J 33. llrtt Hated nap!* vine h^pcrl 19>3. 31. Sin;, Luy k,rm 133 17 2 (71'. W Amm tinn Rcr 2f 30, S tim disorder of prelirmnnrv 133 J 1*3 219 37. fide-, dim o( a Sc, 37:1200 38 Allrn piotonce,! 1 /tint Mod |i TV Kiinpn rndelhrtiOM, iir-Mtenliiird 131 lUMtn. 4(1. Allrn mlrnwopic kevs (ed to1!:7. 41. McC perir^nliti, hnlrornrtM 4-' tVrs nnlnl liiph avi.in rniM- 4.3 l`!< KW. et al N0NS 20<55< ./) .. Kff' , I I11*'1lit,, I *f,/l I,. ,, iii.ilrct i, A Sfed il (lunli G 0O. Iiii-nknr^. Irrmulrr* iirrhnden trL'ftnk* in elder* Ftp li*ol "A: 'Hie i certain loiit tl JSVtlll 1 InHmtf i A: Hip y rril.*in Tofic ilenr* in )<MtAlp<t \ 1942. na|thlha* / Hydro* tMicfttioti Pi: Ocndcljitiia, IS. "hlcrririie JAMA <rf>s)M>sjlo li tArne natology: nhiMuiig tp Verm II: Heniin * (itttirr* ki* f.Sug TOXiJ^LY Of-' IIYUUOCAIfJtuXS--KIAIMtnuok 131 (lilof.iLix1) dim l ililiiiirrle iiiuiiviltiiliti /.vkliwhi t ir r*|o m<;. j^r.7. 11, AjIiiim** KM. Iil'h Dll. Sfu'nirr TiC. cl nl: The rpi]-pti^c of n|J| skill |0 rri>ntlrl Ui hnvp rcut*cri acnrform (k'lTiwIiln. fntluetr hint Surf M*4, Mil. II-UhUT KW, I'mvi IM: i '1 Ihhi Him* 1 |*n|mldm>fhrMcd. hut Afrd S/trg jo :*; jio. ioai. 21. pntind Al\ Sinilli I). Nlrflrr (i, rl nl: A linillh wnvry of in n 2.1 11 p!nt nmf 2.4,f>T i'IjiiO, Arch Known Uvutth PHI. 24. Hnmn W: KIhm-*Io I'.iMiknlitnnijrn wr I'.nl- nlfliHiijt (Iff (*liIfirrtrxr Ifanfnrrt |M-1;fl-J'lOll 2fi, Oiw Kl): Cloracne. Writ J Derm 81.599-f'OO, 1970. 2tV Olafson Ifvi>nker*iln-iix fxilistne) ol cal- llr. Cornell VVf 17 J7D 1'9I. 1917. 27. Ifansel W. Ol'Hon P, Mrl'nlec K: The t*oln- lion and idrnlifmUirto of Hip nnrwSivo agent ol bovine hypretkerAUrd* (xd*cn>et bom a processed wheat rotirpiilrAlc. iVrnr/f Pcf ir> P-l-lfil, 1055. ?p, Hike) 1>, )trjrl|!Ri MK: ^akIiii;* lion of hv|tfrkprMr"'i,< (it^liKpAw' of rMMc with m. rhloiio.ilpil itsidiihidt itc. Scirncr HiVM>i-'!7,, 29. Ihork WH, ,Jone* MW, M-tcVicnr 11, cl aJ: OilnriMMlrH naplirhalrne iiiln\MA<ion In sheep. Atnrr J Vrf Itrt iMWS-tV.0. 1917. !(, Ibiltpr WC, link HP: Tonic effect* of hox* cliioronnplilhdcMC on *Hine, 7*nxc Appi PAerffloeof 4*257.2iV>, 19(12. , ___ , 31. Mtnrllle CK. HpUt KK. Morrill et Kx|Piiiii^nliil firnlMilicm of in rli find hitiMijcri' A*r\tr J VW Vfc l!W. 12. Sikpa P. Wise JC. Mlv. The e*ner- tiiciklnl iitoHiM-lkm of i-riiArnw fhv^icrkPTnlo^ifl) in CAlile with fhlni-inalH n^phlfwlcne* nnd f*lro'euin ftnHuiii J Anttr Vri Ifrrf Aaaor IfkllT Wi, XI Hell WII: HcUlive (okh-Hy of the cblori. nninl n;|Mh;iJrnfa in ctpcrinirntoJly proHiiml bo* vine liv|YrUrAlwit (X'diarnAo). V'rf i/rd 43:3J5*l lOf |nSi\ 21. Snnpet VI, froll U 1 family A. cl nl: Alncn* btry loxrmiA in dikkriw. / Am*t Vti Mrti diw 111:172* 170, IfW. # 3S. AnonyuxKLir Ikr rhipkcikini faclnr. 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Scliulx Klf; Klinivin und rxpcrfmcnleHe tin* tcmichungcn xur AtoJogie dee Clitorame. ArcA Klin Krp farm 206 *W>.r,9fl. 1957. 61. Abelxon PH; PolMinn by organic chemical*. St/cflcc 170:495. 1070. 64. Croaby 1X1, Wong AS. Plimmar Jit el al: Phoiodecrmposhion of rhlmirudcsf rlllwnro^ilicv in*. Science (73:74.1 749, 1971. G5, Crew KD: Clihrnmt. Trane St John Ilutp Verm Sot 60 79-90, 1970. Arch Krwtrun Ueolih--Vul Y5, /lug W72 hWllWPWl MOMS 20S5S9