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ot X. KVilti OH; Vin*r ^ mm MitMin i t'tmi|*itii*n(* i>{ tip*itlivily. Arte i. A: Ktlivt of itifTi-irnl .... Arch Ohtlnrynfi 1 l nkiit* U Jr, rt nt: n jirinmnin. *t!iylrn* \ J. iuinr and ethsnol. V.l, TS'TO. ' Kt-u*lrr CJ: Mcchsme *i,|>uvui* of piinmntfl Health 1S:412- ir, Jwict RA, rt *1: <ourc of labor* tory /if 1`hormotnl 17:?2fi- i Inhxl.illon loilrilin pi i'hnrmetol llir rITft'li of *oro` rieiirrflc innlr on ituxtirlia binculala. C : It iraUUn VI,: llioninlinf air rontami- VU-iJS. 1SXW. of 1wf fonimMchyda um*n orfonum. Gig of *ytnp*lhom imclic of Eip Thrr 127:23- C Kf, at *1: AU/vu` nodr, Arch Intern uf jnhtlnl arrUlilri <*p Thrr 174:14-19, ! of tnhnfrd lirulile- | i Health *4:354-337, abmlty TW. el a|; mat: Sensitive sew .'id estimation and chydrs, Anal Chtm i* fncrrasinf sensl-lonc hvdiuor.e test * nyitca in air. Anal Mucus pnxturlion n vivo slutlies living ii 20 JJO.lTa. 1070. A mrtliDct of deU-'rlie smoke: Ap:ltrm'v. snuMhrtiird end tT24. IMG. . ttvlsmlcr It: NVw| snintM eipe/imrnta: tutuieo smoke bJi'A-MO, ItTJL Toxicity of Chlorinated Hydrocarbons and .Related Compounds A. .Review Including ("tilm inaUd Dibenr.odinxins and Chlorinated l)il)cn7s>fuvanH liennte I). Kimbrough, hi If. Chamhlre. (la * Verlou* chlorinated technical compound*, namely. 2,4,5-trlehlorophenol. 2.4,5-trichlorophenosyecelic jeld (2.4.5-T), and European chlori nated biphenyl* (Phenoelor DPS and riophen A60), have been lound to be conlamin:,,cd v/ith trace amounts ol chlorinated dlbenr durani or chlorlnalad dibenzodioxins. Toxic lat which pro* duces hydroptricardium in chiekift* also contain* chlorinated dibenzodioxlns. These and olher tech nical chlorinated compound* such ** the tech nic*! pcntachlurophenol have been implicaled In causing chloracnt, liver disease, teratogenicity, x-discast in cattle, and chick edema. The lileralur* on the toxicity ol the chlorinated technical compounds is reviewed. It Is mentioned that 2.4.S-T and the chlorinated biphenyls also indue* porphyria. V/hether the various disease enlilies are caused by the contaminants, combinations of the chemical and Its contaminants or by the chemicals themselvas needs further evaluation. RECENTLY several chlorinated com ' ' pounds, such as the polychlorinated biplve. nyl and 2,4.5-tnchlorophcnoxyacetic acid (2.4.S-T), have received a great deal of at . : tention. Polychlorinated biphenyls (PCRl fare increasingly found in our environment and 2f4,5,-T has been used extensively as an herbicide. Occasionally these and other chlorinated technical compounds Iwive caused diseases that bear similarity to each other. Some of these chemicals have been found . to be contaminated with chlorinated diben- zofurans or ciitorinatcd dibenzodioxins. The various diseases produced by one or more of the different technical compounds arc dis cussed in this paper. Attention is focused on tlie various contaminants nnd their possible relationship to different diseases in a variety of species. The need for further well-coordi nated epidemiological and experimental ani mal studies is pointed out. Submitted for public*lion Oct 8, M71; accepted Match 3, iSW. ,,. Krsm the Otamblee Tovicoloey I/lonlory, Envi ronmental Protection Aaency, Chnmbtee. G. Heprlnt rniucib to Oixmbk-a Toxicology labora tory. KnviroruncnUl Protection Agency. 4770 Uu- ford Hwy. Chnmbtee, Ga 30.741 (Dr. Kimbrough), Chloracne tTiis disease is described by the fornvitio.i G: comedones with or without t-ysls and pu.ilulcs. The follicular orifices arc filled with sebaceous nnd keratinous maierial, Melanosis and a secondary inflammatory reaction may exist. Chloracne was described for the first lime by Hcrxhoimcr' in IfiOO who thought it was produced by free chlorinc, Wnucr* in 1916 and Telcky* in lfl27 suggested the term "iwrnakfankhcit." They felt that this skin disease was produerd by certain chlorinated hydrocariwns, Jones and Alclcn* were among the first to report a case of chloracne in a 26-year-old male Negro who worked for three years distilling chlori nated biphenyls. This patient also com plained of lassitude, loss of appetite, and loss of Hbtdo. Chloracne is one of the most frequert forma of occupational dermatitis, and many cases have been reported in the United States as well as in Europe, particularly Germany and England. Tcleky5 reported in 1919 (hot he personal ly had seen at least "150 to 290 workers" in four different factories with chloracne. He stated that liver disease occurs iiulcj/endcntly from chloracne, and usually manifests itself after an exposure time of four to six months, but may occur in as short a time as seven weeks. Occasionally loss of appetite, nausea, and edema of the face and hands are the first symptoms. Abdominal pain and vomiting follow, nnd then jaundice develops. At autopsy, acute yellow atrophy of the liver is found. He cites Flinn and Jarvik1 wlio reported cases of acute yellow atrophy with fatal outcome following exposure lo Halowaxcs. Halowaxrs. which are chlorinat ed naphthalenes, as well as the l'CTl f Aroclors) were increasingly used after 1930 to insulate cables. Tricky' cites many other case reports (Drinker et 1,T Jones.* Croon* burg et alp* Colter,' McLeehtchie and Robertson,1' and Collier1-'). Yon Octtln- Arch Environ Health--Vol 25, Aug 1972 mmn mw 'xiujii fmW7iggjffrTaMey.evnUTVAje.Jt^'jarmkmyvpii7^ HONS 206268 12*; TOSH ttF IfYUtHK'AitlU >Nfi -KtMtttttmau g(.nuii<r.wa3iM describes the occurrence of ^chloracne in workers exposed to these chem* jcnls. He cites several references which indi*cale that dermatitis is the result of the local ^effect or direct contact with the chemical, ^vhde the toxic hepatitis results from absorp tion. pjiloracne has been reported in workers pxposed to chloronaphtha tones, chlorobiphcnyls, cltlorcdiphcnyloxidcs, certain pe troleum products, and solid chlorophcnols.1 * More recently Meigs el at1* and Hofman and Mcneghini** reported 14 and 13 cases of phloracne, respectively. Exposure to eh Ionpaled biphenyls was established in most pf Itiese eases. Birmingham17 observed chloracnc in 15 employees who had painted flat sections of glass with enamel and then baked it. The enamel had Aroclor (a PCB) Incorporated in it. PlcwiB,, produced chloracnc experimentally on the upper back of eight male adults by applying Halowax 1014, pcntadilMronaphthalciie, and hexachlo- jonaphthatonaST Bauer et al1* reported chloracnc in work ers that handled technical 2,4,5-triclilorophciipl. In some of these workers neuromus cular weakness, psychopatbotogical changes, blepharoconjunctivitis, and liver involve ment also occurred. Kimmig and .Schulz9* found that pure 2,4,5-trichlorophcnol did not produce hyperkeratosis when applied to the mhbit car. ( t he ralihit car list is iihiI as a screening lest to determine whether n com|)oiind is likely to produce chlnracne. 31>c chemical, dissolved in pinpylenn glycol, is pnlnlcd on the rabbit cnr. If flintiest is positive, erythema occurs within two days and In n few weeks hyperkeratosis de velops.) The rabbit skin ofTers as an experi mental method that will indicate the ability of substances it produce nenriform derma titis in man.-* Pur 2.4.5-lrichlorophonol did not afTect the r ibbit car, and neither did 1.2.4.5- tclrachlorobcnxcnc. the starting ma terial in the manufacture of 2,4,-r*lrichioro- phcnol. However, technical 2,4,.'i-lnchlorophonol which was used in the production of 2.4.5- T did produce hyperkeratosis of the rabbit ear. It was concluded that by-prod ucts which had resulted during alkaline hy drolysis of 1,2,4,5-tetrachlorobcnr.enc were the causative agents. . Kimmig and Schulz-" isolated several con taminants and found that some of them, namely tctrachlorodibonzofuran f Figure) at a concentration of 0.05% as well ns telrachlorodibcnzodtoxin (Figure) at a concentra tion of 0.005%, produced hyperkeratosis in the rabbit car. A hepalotoxic effect was also observed with these compounds. They also found that pure pcntachlorophcnol did not produce hyperkeratosis of the rabbit car. Chlorscne was observed in workers of a West German plant who produced tech nical pen tachiorophenol from hcxachlorobenzene.*9 The technical material also in duced hyperkeratosis in the rabbit car. It is possible that technical pontachtornphcnot contains toxic Impurities, particularly since pcntachlorophcnol is produced by alkaline hydrolysis from hcxachlorobcnzcnc. Dibenzodioxin and dibciuofuran tliemsclves do not cause liver necrosis or hyperkeratosis when appliod to the rabbit car; however, they become highly toxic when they contain three or more chlorine atoms'* Some of the work ers with chloracne also develop eye irrita tion, hcpatotoxicity, intolerance to alcohol, neuromuscular symptoms, porphyria cuta nea tarda, and psychologic alterations.-3 Ac cording to Braun,3* chloracnc seems to re sult from direct contact with the chemicals producing it. Crow,** on the other hand, points out tliat chloracne can also be pro duced by systemic absorption. Arch Environ Health--Vol 25. Aug 1972 'Hits tils. Olafson** it ilcnce was clilof innlnl ease.*1 Call decline in toms of poi,1 lion, diftrrh and dischat sough, poo maculae in hypcikeral* scopic era shows cent cells with ' lion of the bladder. C tubules of degiee of fi pancreas, i crosis and the nephre the endomi after ingechlorinate? Link1" fed swine and the liver a: vaginal cp A depressi was also o Drinker liver of r mals were naphtha lei hcxachiorc phenyls. ' chloronnp! to modera with cenl cells. Degt the kidne; tosis. It can that high duce live cows, x-d drop in tl the Icadii is possib represent liver dire Sikes e produced jmim srwKigmsttsa'JuusiijiaJJsrwjWiW JHJWiiUMJHkWBP HONS 206269 / r^,,-thcT n .-ftlcrnme. '.1,Wci>r glycol. If tiic tcsf is hilt (wo days jrfcrrutosis do ts* nn cx|>crido the ability , ifonn dermaj(oi|i|\cnol did 1 neither did starting nn,4.5-trichloroi,4,5-lricli)oroproduclion of rntoeis of the I thill by-prodp alkaline hydtenzenc wero id several conAmo of them, Jii (Figure) at [4*'H as tetraj st a conccnlrn- ' frkcralosis in ac effect was ground*. They rophcnol did Ihe rabbit car. corkers of a deduced tech^ hrxachlororrial also in dibit car. It is fchlorophcnol icularly since d by alkaline -irenc. Dibenoselvcs do not rralosis when iowover, they jeontain three j of tlie worki>p eye irrita.-c to alcohol, iphyrin cutntralions.21 Aci seems to re(he chemicals j other hand, { also be pro- It @ naphthalene*. ip^il^i uiih [wlruli iuii_jkjnI uels Mich (1-S rr;ht e:i-o mi. Hie loiir pr'ixl- This disease in cattle was drscrilicd by itcts m re excreteST.?w milk .iiiiI produced Otafron-* in 1SM7. A few years taler evi x-discasc in the enh-rs drinking ~lhrT~m>lk~ dence was published showing thnl highly They cited other mitlmr.s who wore nhle lo chlorinated nuphtlvilrnrs caused the dis- produce the disease with a complex wood ensn.5? C-itUc with x-ilist-asc ,sitow a rapid preservative nnd n Itilirimnl. dcclino in vitamin A plasma levels. Symp Bell23 tested the ability of various com toms of poisoning inch)tie excessive Incrimo pounds of the chlorinated naphthalene tion, diarrhea, polyuria, marked salivation, group to produce x-diseasc. He discovered and discharge from tlic nostril*. A ciironic that dichlorinnlcd nnd trichlnrinatcd naph cough, p>oor apjielito, and numerous' red thalenes did not produce the disease, while maculae in the buccal mucosa develop, and tetrachloronaphlhnlouc had an effect, and hyperkeratosis of the skin follows. Micro the higher chlorinated naphthalene, penta- scopic ' examination of autopsy material chloronaphlhalene, ;><x.achiorornphthnlene, shows central lobular degeneration of liver hcptachloronnphth- icnc, and octadiloronaiih- cells with bile duct proliferation and dila thalcne, caused severe disease. Oetnchloro- tion of the glands in the wait of the gall naphthalene was lens toxic thon hexachloro- bladder. Cystic dilation of the collecting naphtholcne and hoptachloronaphthalcno. tubules of the renal cortex, with a moderate degree of fibrosis and degenerated cells in the . Chick Edema pancreas, was also observed.2* In sheep, ne crosis and cirrhosis of the liver, damage to In 1957,*4'5* a disease occurred in a large the nephrons, and squamous metaplasia of number of chickens which, at first glance, the endometrium were the principle findings seemed to represent an epidemic. It was after ingestion of feed containing highly soon discovered that the residues of certain chlorinated naphthalenes.2* Huber *and distilled animal fats produced the condition Link10 fed hcxachioronaphthalcnes to young when they were added to the chicken swine and produced degenerative lesions of diet2*-" The disease was called chick edema the liver and kidneys and hyperplasia of the because it manifests itself with hydroperi vaginal epithelium with keratin formation. cardium and ascites in chickens. Ducks and A depression of the vitamin A plasma level turkeys experience a reduction in growth. was also observed. Allen and Lalich1* produced hydropori* Drinker and co-workcrsT found that the cardlum and ascites in chickens when liver of rats was affected when the ani enough toxic fat was given to kill most of mals were fed high doses of tetrachloro- the birds in five weeks. ('Toxic fat" is a nnphthnlene, pcntachloronaphlhalene, and term used for fat found in chicken feed that hcxachloronaphthalcnc or chlorinated bi induces chick edema.) When the concentra phenyls. When Schocttle et al51 fed hexa- tion of toxi6 fat was reduced and fed to the chloronaphthalcne to rats, they observed mild chickens for ISO days, hydropcrcardium and to moderate fatty degeneration of the liver ascites developed less frequently, but testicu with centrilobular vacuotalion of hepatic lar hypoplasia became apparent. Simpson cl cells. Degenerative changes were observed in al1* described proliferation and hypertrophy the kidneys and the skin showed hyperkera of the vascular endothelium and possible tosis. necrosis of hepatic and bile duct tissue in It can bo concluded from these reports chickens and turkeys. When monkeys (A/a- that highly chlorinated naphthalenes pro coca mulatto) were fed toxic fat, alopecia, duce liver changes in several species. In subcutaneous edema, decreased total scrum emn, x-disease of the akin, together with a protein (with a reversal in the albumin-glob drop in the vitamin A plasma level, is one of ulin ratio), and reduced hematopoiesis and the leading manifestations of the disease. It spermatogenesis dcvclojicd. Gastric ulcere is possible that tire vitamin A deficiency occurred in 66% of the animals. Focal areas represents a manifestation of concomitant of necrosis and degeneration were observed liver disease. in the liver; and the bile duct epithelium Sikes et al12 found that x-disease could be, was found to be affected when it was exam produced in cattle with highly chlorinated ined under the electron microscope. Dilala- Areh Environ H<aUh--Vol 25. Aug 1972 MONS 206270 p*------------------------- ----------------------- / TiWi 3- Oiic im Rctultlng Vrom E ipotun ChWKM Orlun petiokwn pfodvcti Oktororapfhthilctitft (mainly (Mftli. htii, and hfptl) Chlo#olph*nyL ChlerOdiphenyloiaJe* Chloroplirrii| (Itchrveal 2.4,5 tnchlorophen!. penlacMorophanot) Technical 2,4.5 T 1 Ml. Ur.f Slrlh C.l.cli *n4 l.lh.l Factor Chlorinated naphthalene* Certain technical 2.4.S-T Chlorinated biphenyls rvrilied miteriel Technical 2,4.5-T and from lo.lc (( other tMorophinoli Polychlorlnited biphenyl* X*Oltaae In Caltla Highly chtonna led naphthalenes Petroleum oro'lvtlt - . * "Toitc Ur li a farm used for fat found In ch<Mn feed mat Inducti chick edema. tion of the heart and hypertrophy of the cardiac muscle were also present.46 Toxic fat is not the only product capable of producing the chick edema syndrome. Chlorinated biphenyl products, used as a ptasticir.cr in a paint, have caused hydroper icardium and ascites in chickens,41 and two of seven Bengalese finches fed PCB de veloped hydropericardium.45 The seven finches of a total of 5G birds died during the course of the experiment. A mixture of pentnchloronnphthnlenc and hcxachloronnphlhalenc, when fed to chickens, resulted in chick edema.45 The toxic fat which contained the chick edema factor was studied intensively. Flick et al`* separated a purified crystalline concentrate which produced chick edema and decreased the hatchnbility of injected eggs. Embryonic deformities were also produced. Flick et al45 were not able to produce testic ular. hyjioplasia in cockerels when they fed low doecs of toxic fat (0.6% and 1.0%) to the cockerels for 12 weeks, as had been re ported by Allen and Lnlich.5* In 19G7, Cantrell et aiM reported that 1,2,3,7,8,9-hexachlo rodibenzo-p-dioxin waa one of the toxic compounds producing chick edema. Tomita et altT had shown earlier that the heating of pcntachlorophenol pro duced octachlorodibenzo-p-dtoxin. Higgin botham et al1* showed that the chick edema factor represented chlorinated dibenzo-p-dioxins. The te*7 principal compounds iso lated were %3,7-trkhIorodibcnzo-p-dioxin and 2,3,7,8,-tctrechlorodfbenzo-p-clioxin. The authors suggested, as a possible source of contamination, fata and fatty adds contain ing commercial chlorophenols. When crude fats and tallows are heated to produce fatty acids chlorophcnol residues might be con verted to a chick-edema factor. It was mentioned earlier fn this article that the Aroctors con produce chick edema. The Aroclors (PCB) arc used primarily ns dielectric fluids for capacitors and trans formers, as industrial fluids for hydraulic, for gas turbine and for vacuum pumps, and as heat transfer fluids. They are also used as plasticizers and are widely distributed in the environment.4* Aroclor is a trade name un der which these compounds arc marketed in the United States. They can be found in synthetic resins, synthetic and natural rub bers, cellulose resins, paint varnish, wax, asphalt, and in allyl starch. They have been employed for dust prevention, moisture proofing, sealing, impregnation, and vapor suppression to prolong the residual life of insecticides. They increase the toxicity of dicldrin and DDT in insects.** Depending on the amount of chlorine they contain they are assigned certain numbers. Aiodor 1260 for instance, contains 60% chlorine, white Aroclor 1242 has an approximate chlorine content of 42%. Miller,*1 in 1944, tested a commercial chlorinated biphenyl with 42% chlorine and observed liver damage in rab bits, guinea pigs and rats. Skin changes were observed in the animals who received subcutaneous injections and application of the material to tho skin. The skin lesions produced by subcutaneous injection were histologically similar to those of chloracne in man. Direct application to the skin pro duced inconsistent lesions compatible with low-grade irritation. Von Ocllirgen,,(reiw-3ri discusses some of the earlier work on the toxicity of tho Arodors in his book The Halogenated Hydrocarbons, Toxicity and Potential Dangers. Nishizumi15 observed changes in the liven of mice and monkeys after feeding them chlorinated biphenyls. The author undertook this work because of an outbreak of poisoning that involved at Arch Environ Health--Vol 25, Aug 1973 to Technics! Compounc 1o(C f||* Chfftnnittd biphtr Mnlvff ot pfMlC^ fllpMMkn* and hea#chloio niphlMlvnt least 600 people ingested rice bra inaled with et FCil i KanccMo leaked into the holes in 3 pipe i manufacturing mentation and brown pigment bom and nev, h Stillbirths were of the mother. . orexia, fatigue, like discharge and dnrk-broui Vos and Koe several polyehI cns. quail and the toxicity ot polychlorinatc*and Clophcn A which was pro The European toxicity and pr crosis. Chick c with Kurepeat Aroclor 126(>. duccd porphyn. three compour benzofuran, pc hexnchloronapl the European *. from the Unit* cordium occur Aroclor 1260. indicative of s tor in this pro' Recently. F Bclhcsda, Me HONS 206271 frk edema. trfma'rily as ^ and Ironshydraulic, imnips, and 4iteo used as 4<utcd in the je name uninarkelrd in 4? found in Natural rub- -nlsh, Wax, i have been t, hioisture a and Vapor : uat life of i toxicity of JDcjx1tiding i 'nlnin they toclor 1260 i -inc, while c Chlorine 1, tested a ! with 42% ge fn robn changes `0 received iliention of 4tn lesions /lion were -i rhlorarne 1 skin Jiroitible with lHlhMSHII ;rk on the ibook The i icily and i observed J monkeys biphenyls, because of evolved at F--------- - European ctitoftnatoe bipScnyii (fhtnOClOf 0P6 #nd CtOphcrt A 60) ' LllUd in Tbl 1. T*tf*cMor&dtbfiforuf n ^entichlpf9(Jlb(rtfo(iirin HaeMo'OrtaeMhlefie least 600 'people In Western Japan who had Ingested rice bran oil that had been containmated with ciilorobiphenyls, a Japanese PCll (Kancchlor 400),! The clrlorobiphonyIs leaked into the rice bran oil through pin holes in a pipe used for hent exchange in the manufacturing process. An increase in pig mentation and abnormal grayish darkbrown pigment deposits in the skin of still born and newborn infants was observed.41 Stillbirths were unrelated to PCB poisoning of the mother. Adults showed dilomcne, an orexia, fatigue, edema of the eyelids, cheese like discharge from the meibomian glands, and dark-brownish pigmented nails.14 Vos and Kocman11 studied the toxicity of several polychlorinated biphenyls in chick ens, quail and rats. The authors compared the toxicity of two European commercial polychlorinated biphenyls (Phenoclor HP6 and Clophcn AGO) and one {Aroclor 1260) which was produced in the United States. The European compounds showed higher toxicity and produced ccntrilobular liver ne crosis, Chick edema was a common finding with European compounds and rare with Aroclor 1260. All three compounds pro duced porphyria. Chemical analysis of these three compounds revealed telrachlorodibonzofuran, pcntochlorodibenzofuran, and hexachloronaphthalene as a contaminant in the European samples but not in the sample from the United States.** Since hydropericardiup occurred occasionally In chicks fed AroctMrl280, the authors felt that this was indication t small quantities of a toxic fac tor In this preparation. by Emerson ct al5T found e teratogenic effect of technical 2,4,5-T in rats. Apparently, the technical 2,4,S-T was contuminatcd with 27 ppm of 2.3,7,8-lctrachlnr<vliJ)enro-p-dioxin. In the study published by Courtney ct nl,'* it was stated that the technical 2,4,5-T which was found to be teratogenic in two strains of mice and one strain of rats was con taminated with 30 Pf>m 2,3.7,8-tclrachlorodibonzodioxin. Emerson ct aR tested 2,4,5T that only contained 1 ppm 2,3.7,8-lctrachlorodibcnzo-p-dioxin at comparable dosage levels and did sot elicit a teratogenic effect. This finding was substantiated by Spnrschu at al53 who studied teratogenic effect of 2,3,7,8-tctrachlorodibonzu-p-rlioxin in the rat A slight effect was observed at a (lose of 0,125/ig/kg/day when the material was giv en by gavHgc from day 6 through day 15 of gestation. At the level of 0.5;*g/kg/day, Ute effect was quite pronounced. Courtney and Moore4* were ablo to produce cleft palates and kidney malformations in three strains of mice with high doeos (100 mg/kg subcuta neously daily from day 6 to 15 of preg nancy) of analytical grade 2.4,5.-T that contained less than 0.05 ppm 2J,7,8-tclrachlorod ibenzo-p-dioxin. Keplinger et al*1 reported a decreased survival of pups in rat reproduction studies when fed 100 ppm of Aroclor 1242 and 1254, and poor hatchability of eggs from chickens fed 10 or 100 ppm of Aroclor 1242 or 100 ppm of Arochlor 1254. It hns been said11 that a purified crystalline concentrate from toxic fat led to the development of embryonic deformities in chickens. Tcr*logenesIs Comment Recently, Bionctics Research laboratory, In some instances, the same chemical com Bethceda, Md (unpublished data), as cited pounds are responsible for the occurrence of Arch Environ Health--Vol 35, Aug 1972 O130 :ivrry df tt\t)i;ocAtiii(iNs--i<nttm\x;:ti t chloraciic in people, liver dispose in sevrnil specie*, x-discasc in coltlc, chick rclrmo, nnd teratologic or other effects on (he fetus. Not all of the disease entities hove thus for been produced by nil of the compounds (Table 1). Some of the compounds in question hove been shown to be conlnminnled wilh chloriruiled dilfnzo-p-dioxins or chlorinated dibenzofurnns i Table 2). The decree of con tamination seems lo vary wilh different compounds. Some companies manufacturing these compounds have instituted dean-up procedures which remove the greatest part of the contaminants. Improved hygiene among the workers and improved ventila tion of the working area have, in many instances, reduced the incidence of chloracnc. Whether all disease entities described are caused by the chlorinated dibenzodioxins or the chlorinated dibenzofurans is not yet known. Some of these chemicals arc highly toxic, as illustrated by the fact that two applications of 10pg of 2.3,6,7,-tetnichlorodibenzo-p-dioxin applied to human skin*1 produced chloracno-Iike symptoms. Single oral doses of 20,,g lo 50pg/kg/body weight resulted in fatal liver necrosis in rabbits.*3 There is no readily available information on the metabolism of these compounds In animals and their breakdown in the environment.*3 It is probable that they are stable. Crosby et alr< found that 2,3,7.8-letrachlorodibcnzo-p-dioxin and its homologuos 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 are the result of one or sev eral contaminants or the combined elTect of the ehcmTeal compound and its contaminant. Another unsolved problem is the observa tion that some of that compounds such as technical 2,4.5-T Induce porphyria.*3 The chlosKated biphenyls also cause porphyrla.**fc Whether porphyria is the result of Ojcftemicals themselves or ol the con taminants, or both, is not known. Crow*3 suggests that the porphyria produced by technical 2,4,5-T may have been caused by contamination of the chemical with crude chlorobenzenes, which were used to produce the chlorophenols Irom which the 2,4,5-T was made. Better awareness of the possible ctmfaniitt.'ilion of (he lechrtirul ihi'inicfils wilh various highly toxic sultst-inces, well coordinated epidemiological studies, nnd ad ditional experimental Ktudic* in Animals are needed to clarify these problems. Chloracnc has Ix-en produced rxjierinirntnlly in men by Shelley find Kligmnn (Arch Derm 75:689, 1957). The nutlvirs cite addi tional references on cxjierimenl:il dermal ex posure 'if animals and men to chlorinated naphthalenes. References 1. Herxheimer K: Uber Clorakne. Munch Mrd WrAr 46:278. ISM, - 2. W*utr H: CewrrWichr Erkrwkunirn dutch *eehlorl Kohlenwaucisloffe. Zbl Gem tty* 6:100, ISIS. . 3. Teleky L: Dio PirrulimUifit (Chlonkntl. Klin Werhr 0:845-848; 807-001, 1027. 4. Jones JW. Alden HW; An erneifnrm dermaler- Arch Derm Syph ,H;I0M.I0H, III3C, 6. Teleky Ic Uber Newer Knrvrhimjt-nirlhoden und Fomrliuneen auf dem Grhicl drr Cr--erbe kr.nk- heilen, Klin W.chr 27:240-257, m4`J. 6. Flinn FIJ. Jarvik NE: Actions of certain chlor- innled nnphthnlcnen of the liver. Proc Sue Ezp Dial Mrd 35:118-120. 1036. 7. Drinker CK. Wimn MF, Bennett GA: The problem of potafble ayatemie (Hla from rertain chlorinated hyilroraibona, J Induct! 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