Document Q8nrogww3eL2Y7D6RQkJObw4

NOTICE:' Thia material k?? bo protootod by copyright tm iriinwi util! Ut utlh l'i r\pt t Hi < \ Yu! rt>. 191-tvS I97S General Summary and Comduskins by DHEW Subcommittee on Health Effects of PCBs and PBBs * ` Chemistry The great complexity of PCB commercial mix tures has provided the difficult task of separating the components of these mixtures and determining the complete identity of the compounds Efforts to define these mixtures have been quite successful over the past several years (/). Identification of the component chemicals in PCB residues presents another difficult problem. Little progress has been reported in this area. Since the fate of components of commercial PCB mixtures entering the environ ment cannot be followed directly, inferences must be drawn about chemical alteration of chlorinated biphenyl compounds m the environment mainly based on laboratory studies. The known resistance of aryl chlorides to chemi cal oxidation and hydrolysis presumably was a mitior factor in the promotion of PCBs for industrial uses. Exposure to nonmctabolic environmental agents is unlikely to result in significant oxidation or hydrolysis of chlorinated biphenyls. However, since appreciable photoalteration of chlorinated biphenyls has been observed using either sunlight or sunliglit-simulating lamps in the laboratory (/) as energy sources, it is highly probable that photo chemical changes occur in the environment. These photochemical studies have indicated that icductive dechlorination to biphenyls of lower chlorine con tent is a predominant alteration route although for- * Member! of the Subcommiliee: A. C. Kolbye (Chairman). Food and Drug Attminbirjlion, IW C Si., S. \V,, Washinipon. D C. 20:W; J. L. Buckley; ). Burke. F. Cordle: P. Corncliu!left; D, Firestone; L. Iishbcm; G, Fhmm. G, F. Frit!; A. Gardner; L. GjitholT, H Gerslner. J. A. GoldMein; U. ttaektey; C. F, Jttmek; L. Kasw; R. Kimbrough; T, E, Kopp: V. Ku, R, L- Lcluo."'''. W Marcus; tt, 11. Milihcwi; J. D. McKinney; J. WcUiugtitin; J. A. Ktoore; I I. Pomcraniz, R. A Rhoden: J A Ko.ich: S Shiltlo; R E, Shapiro, R. H. Teste; and W, Troller, mation of more polar compounds, including a chlorinated dibenzofuran, has also been rcpoi ted (/, 2). The diverse conditions of the environment make it difficult to predict accurately the end products and rates of photonlteiation of chloi mated biphenyls. From a comparison of carbon-halogen bond energies, brominated biphenyls might he ex pected to be more readily altered by light than chlorobhhcnyls. But because of the lower volatility and different end uses of bromobiplienyis, they may not be as readily exposed to light as the chlorinated analogs. A typical PCB residue from fish resembles the Aroclor 1254 mixture more closely than it does other Aroclors CL 4). Considering the major com ponents of Aroclor 1254 (5). it appears trial pentn-, hexa-. and heptachlorinalcd biphenyls tend to con centrate at this trophic level in the biosphere. It is of considerable interest, therefore, to carry out com parative accumulation, metabolism and toxicity studies emphasizing these higher chlorinated biphenyls using compounds of known clilonnc sub stitution pattern. Individual chlorinated biphenyls arc now quite accessible through synthesis and re cent studies have begun to obtain these types of biological data. Studies with the use of a group of five symmetri cal hcxachtorobiphenyl isomers in chicks t(5) and in mice (7) indicated that distinct difference in toxicity are possible and these differences could he related to structure. The isomers with chlorine substituents in the 4,4' positions appeared to accumulate moic rapidly in adipose tissue and showed increased ac tivity in the liver and greater overall toxicity (<5. <S). Comparison of two pcntachlorobiphcnyls m laving chicks again indicated the one isomer with 4,4'subxiilution to have greater toxic effects (V. 10). Structure-activity relationships, particularly for biphenyls known to be major components of com- mctcial PCB mixtures, could he useful in assessing the potential hazard of these compounds, June 1978 191 HONS 206401 A major part of deici mining human exposure lo A range of Cl-DBFs (from dichtoro through PCU lesuloes in foods is evaluating the adequacy of hcxachloni) have been reported in v.inous Aroclors Use analytical mctiuTdology used and the signifi (IS. 16) and two specific compounds, the 2,3,7,S- cance of the data obtained. The methods applicable tetrachioro- and 2.3.4.7,g-pcntuehlorodibcnzo* to PCIi determination ,m` complex and to be judged furans. have been identified (17). Quantitation of Adequate should give acceptably repiotfucible ic- Cl-DBF contaminants m PCD mixtures, a difficult sulls in tile hands of experienced analysts-. The de procedure, suggests total CI-DBF levels in the low gree of success of inicrluboratoiy collaborative parts per million range (16, 16). The presence of studies helps menstne the adequacy of a method. Cl-DUF in a synthesized, individu.d, symmetrical PCD residues me multicomponent mixtures chlorinated biphenyl has been reported (19). Many common cliloi in.ucd pesticides me exliactcci Chemical analysis of these individual from samples along with the PCBs Pioccduics for chiorobtphcnyls may be necessary prior to their use separation of PCIi residues from interfering pes in toxicological and other biological studies. ticides thcicforc become impoitant as a prerequisite There have been no published positive findings of lo quantitation. Sevctal dilfcicnt quantitation tech Ci- DBFs in enviionmentnl samples or in roods other niques have been used (/). Companion of PCB than rice oil, 7 he finding of Cl-DBFs in such sam residue data is difficult where standardization of (he ples would not necessarily implicate commercial quantitation proccduie is lacking. PCBs as the source of these contaminants, since It has been show n that recovery of PCB mixtures Cl-DBFs (gcnemlly the higher chlorine levels) have purposely added to food samples, using commonly `been reported in other industrial chemicals (20-22). applied analytical methodology, vanes with the av U is also possible that Cl-DBFs may be formed or erage level of chlorination. Recoveries tend to de altered in the environment. crease with increasing chlorine level (//). Analytical ptocctlures for determination of PCB and PBB (the latter is predominantly a hexa- biomobtphcnyi) icsidues arc essentially similar. Metabolism and Biochemical They differ somewhat in cleanup of the extract and Toxicity in the use of u higher column temperature for gas chromatogiapbic determination of the PBB residue. The effect of PCBs and PBBs on the hepatic The limit of quantitation for PCBs is generally 0.2 mixed-function oxidase (MFO) enzymes has been ppm for individual foods and about 0.05 ppm for the most thoroughly studied of any biochemical pa total diet composites based on Food and Drug Ad rameter that they arc known to alter. On a molar ministration methodology. For PBB residues, the basis, the PBBs arc approximately fivefold more limit of quantitation is approximately 0.05 ppm in potent than the PCBs in inducing increased levels of fatsandO.OI ppm in nonfatty foods, fntcrlaboratory the MFO enzymes (2i). Among the PCBs it appears studies of analytical methods for PBB determina as if their potency increases with increasing chlori tion have not been reported. nation and chlorine substitution in thcpuni > ortho TSte cliloiinalcd dibenzofurans (Cl-DBFs) have > mela positions respectively (2d) However, this become a focus of concern as the class of contami induction of the MFO enzymes is not unique to nant compounds in commercial PCBs most likely to these compounds, and the induction observed is contribute significantly to the toxicity of the PCB well within the range observed with many other mixture. This concern presumably stems mainly xenobiotics. The PCBs are somewhat unique as from the demonstrated toxicity of 2.3.7,8-tctra- MFO inducers in that they induce the formation of chloiodibcnzo-p-dioxin and the similarity in struc both Type I and Type tl P-450 (2.5), but this induc ture between dibcnzo-/>-dioxin and dtbenzofuran tion may have been due lo the fact that Ihc commer {12) and fioni the few' toxicity data that have been cial formulation used in the study was a mixture of published for CI-DDFs {13). Recent data indicated twenty or more PCBs which were metabolized to an the toxicity of 2,3,7,8-tctrachlorodibcnzofuran ap even greater number of metabolites. In addition, proaches that of the analogous dibenzo'/x-dioxin. at many, if not most commcicial PCB formulations least in clucks and in guinea pigs (N). If (he chlori- contain trace amounts of chlorinated dibenzofurans vrated dibcitzo'p-dio.xins can serve ns an example, (26), These compounds may be up to 170 times chlcuinatcd dtbenzofuran toxicity can be expected more potent as MFO inducers than the PCBs. The to vary with number and position of chlorine atoms chlorinated dibenzofuran conccntmlion of Ameri on the parent ring system. Relationships between can PCB formulations is usually quite low when structure and toxicity xvill cmcigc as more Cf-DBFs they arc produced: however, (he effect of long-term arc synthesized and tested foi toxicity. exposure is unknown. In any ease, since induction m Envlr<mmciUal HcjiHIi Pcrapcciitcs MONS 206402 i i \ I I t I of the MTO enzymes may result in increased hor mone metabolism ur caicinogcn ,ieiiv,ition. expostirc lo the PCBs and PBBs sliould be limited on that basis alone. PCUs and PORs administered arc relatively high concentrations, usually 50 ppm or higher in the diet, lo laboratory animals have been shown to cause porphyria (27), disfunction of the lhyroid (28). inhi bition of vmious enzymes (79), changes m the liver to body weight ratios (30). vanous disorders of the liver (31), and to alter the level or utilization of cor ticosteroids (32), and vitamins A, D, and E (33-35). Certain of the less chlorinated PC 13s have also been shown to have a nuhl estrogenic effcci when tested in the immature rai and mouse (56, 37). However, most of these paiamctcrs have not been studied in sensitive species or demonstrated at low exposure levels in laboratory animals. The available data imply that the PCBs and PBBs containing six or fewer halogen atoms arc readily absorbed from lhc gut of highci animals.'The avail able data also imply that the PCBs ,nc not excreted to on appreciable extent prior lo metabolism to more polar compounds, and that long-term PCB storage is in the skin and adipose tissue [38). Studies of PBB metabolism arc not yet available. Since tis sue samples from birds and mammals with known exposures to PCBs usually contain only those PCBs with five or moie chlorine atoms, it is assumed that the less chlorinated PCBs have been metabolized and excreted. On the other hand, there is little evi dence that fish can metabolize any PCB, and an analysis of fish tissue usually shows a PCB pattern very similar to that lo which the fish were exposed (//> Laboratory studies have demonstrated that the rale of PCB metabolism and thus excretion is ap proximately inversely proportional lo the degree of PCB chlorination so long as (Inc are two adjacent unsubsliluted carbon atoms on the biphenyl molecule. When two adjacent unsubsliluted caibon atoms arc not present the biological half-life of the given PCB may be a matter of years and accumula tion of high tissue concentrations with continued exposure is inevitable tfJt). It should be noted that the msgor constituent of FireMnsicr BP-6 docs not have two adjacent unsubstitmed carbon atoms and that the corresponding PCB has been shown to have an extremely long half-life in the lubointory rat and probably the human population as well. It should also be noted that metabolism can also result in fuithcr complications of the PCB problem, because those PCBs which aic most readily metabolized and excreted arc those which are most likely to be metabolized via arene oxide inter mediates. Whereas the reactivity of arene oxides varies greatly ami often ultimately iktenuities the toxicity, inui.igcmcuy. ot c.ucinogcnicuy of liic parent compound (19), the PCBs offei such a range of dcgicc and position of substitution lh.it it would not be unlikely to find dial one or moie of these PCB metabolites would have the proper subduy lo be a mutagen or a carcinogen Thus a move fiontthe more highly chlorinated PCB formulations to the less chlorinated ones may help solve the long-term residue problem only to intensify other pioblcms Animal Toxicology Gleaning the information that is now available on animat toxicology makes it obvious (hat different commcicial mixtuies of PCBs elicit diffeicnt love responses in animals, and that different animal species vary in their susceptibility to the' toxic ef fects of PCBs, Reproduction is severely affected m mink at a dietary level of 5 ppm Arocior 1254. and n slight effect is still noted at a dietary level of t ppm (40). In rhesus monkeys reproduction was reduced at a dietary level of 2.5 ppm of Arocior 1258 (4/1 [n rats a dietary level of 20 ppm Arocior 1254 de pressed reproduction, while in the same rr.l stiain (Sherman), in a study conducted simultaneously m the same laboratory, a dietary level of 500 ppm Arocior 1260 was nccessaiy to reduce reproduction (42). In comparative studies done with European products. Phcnoclor DB6 and Clophcn A60, and [he American product. Arocior 1260, the European products were more toxic to chickens than the American product (45). The difference in toxicity in this study was attributed lo contamination of the European pioducls wilh chlorinated dibenzoTurans and perhaps chlorinated naphthalenes. However, il the differences m the effect on reproduction by the diffeicnt Aroclors are compared, the contamination with chlorinated dibcnzofui tins may not be the deci sive factor. Hepatic porphyria has been produced in a number of species, namely the chicken, rabbit, Japanese quail and rat, by a number of commercial mixtures, such as Ctophen A60, Phenoctor DP6, and Aroclors 1016, 1252, 1254, and 1260 (27, 43^6) Hepatic poiphvria has not been repotted in the monkey, mink, or human, which arc species quite susceptible to the toxic effects of PCBs in other ways. Arocior 1254 and Arocior 1242 produced he patic potphyria in the female tat at doses lower than Arocior 1016, Again, diffei ent commercial mixtuies produce this toxic effect at different dosage levels. The hcp.tiie poiphyiia occurs concomitantly with an increase in ALA synthetase in the liver Mixed function oxidases are also induced m the tivci and comparative studies with PCB isomers have June 1978 ` 193 MONS 206403 suggested dial if [lie 4.4' positions on the biphenyl ring nrc occupied by clilunnc atoms [lie effect is most pro no 11 nee i! (47). The liver K the primaiv target oigan foi PCBs in (he rat. !i,irly changes include hepatomegaly, with a concomitant incicnsc m smooth endoplasmic iclicnlitiii, lipid accumulation at higher dietary levels (20 ppm fbi Aioclor 125-1 and 1260). and idirasimctural changes such as atypical mitochondria and tlie formation of "fingerprints" (concentrically ar ranged membranes mu rounding lipid vacuoles) in the hepatic cytoplasm. An incicnsc in mitotic fig ures and cell brenkdou n arc sncieusmgly noted vnh cithci higher (loses or longer c.xposuic {48) These changes arc not as pronounced with Aroclor 1242 or 1016. Similar changes have been rcponcd in the primate (4/). In the mouse, liver tumors have been produced wilh Aroclor 1254 (49) and Kancchlor 500 (50) and in the rat w.th Kancchlor 400 (5/) and Aroclor 1260: Some tumors have also been produced with Aroclor 1242, 1254. and 1260 (52) m rats in a separate study. In one study with Aroclor 1260. some of the tumors were classified as hepatoccl' ilar catcmomas (JI). The dietary levels of the PCBs in all of these studies were 100 ppm or more, a high level when compared to the daily average human intake of PCBs but not Yery high for subgroups with a high intake of fish from polluted waterways or tn some occupational situations. This is emphasized by the fact that the dietary levels which produce tumors and the lela(ivcly low dietary levels which affect reproduction (2,5 ppm in the monkey and I ppm m the mink) of some commercial PCB mixtures do not represent a no-cffcct level. It is presently not known what the no-effcct levels me. Other uncertainties contribute to these problems. The Yurho oil which caused a poisoning outbreak in Japan was not only contam inated with PCBs but also with high levels of chlori nated dibenzofumns. - In (he primate, in addition to the effect on the liver, the gastric mucosa (5.7), the skin, and the Meibomian glands arc also affected at compara tively low dietary levels and the bone marrow is depressed (41), while the gastric mucosa of the rat is affected only at exceedingly high doses '(49). Whether the dog also shows an effect on the gastric mucosa needs clarification. In the rabbit, atrophy of the thymus is a toxic manifestation in addition to liver pathology (44). Fluid accumulation occurs in primates, chickens, and finches. The lymphatic system is also affected in minks. ` The few studies conducted with some hexnchlorobiplicnyl isomers demonstrated that the 3t4,,5t3't4')5'-hc.\nclilorcihipticnyl was the must toxic while 2,3,6.2',3',6`-he.xachloiobiphonyl was (lie least toxic isomer (7) Penta-. hc.xa-. and heptuchlorobiphcnyls arc prefeicniially re tinned in mammalian adipose (issue foi extremely long periods of lime (48) at fanly high concentrations in thciatfoi a rccovciy period of 16 months Whether this has an influence on the toxicity of PCB mix tures has not been determined. The toxic effects of the contaminants of PCBs have not been extensively studied While it is as sumed that chlounated naphthalenes arc toxic within the same dosage langc as the chlounated biphenyls, the chloimated dibcnzofuians piobubly have a gicater toxicity It is assumed that 2.3,7,8letrachlorodibcnzofui.in is the most toxic of this group of compounds This compound also shows marked species v;u lalion. While the single oral LD-,,, in guinea pigs is between 5 and 10 /jg'kg body weight. 1000 gig/kg 1 CDF given orally had no effect on rats. Mice ate equally insensitive to the toxic effects of TCDF (14). For the brommntcd biphenyls, limited toxicity data arc only available on mixtures containing pre dominantly hexa- and octabromobiphcnyl. Both mixtures differ sufficiently in isomeric composition so that their toxic effects may quantitatively be quite diffcicnl and also different from the PCBs. Again, the problem of toxtc contaminants has not been resolved. If toxic effects are similar to PCBs then, at least in some species such as mink and monkey, long-term tow-lcvcl exposure should result in measurable toxicity. Additional animal studies are needed to resolve some of these problems. Poor metabolism and excretion of the brominnled biphenyls may lend to long telcntion of these com pounds predominantly in adipose tissue wilh ac cumulation to very high levels on continued expo sure. Whclhci this would lead lo sufficient iccirculalion of the chemicals lo cause toxic effects on target organs is presently not known. Human Exposure Several reports (54-61) pioVidc evidence that would indicate that a substantial proportion of the population of the United States has been exposed io PCBs. Minimal human expostue of the population to PCBs has occuried from food, air and water, while significant human exposure appears to be limited lo spoils fishermen consuming ficsh water fish from contaminated streams and hikes, and to occupational exposure in industrial workers. Jclinck and Corncliussen (54), in reviewing data from the TDA Total Diet Study 52), icpon that all food classes of the total diet declined to no PCB occun cnees except in these nicai-fish-potihry com posites. About 409r of these composites continue to 194 Environmental Health Pcrxpcctlses HONS 206404 contain detectable residues of PCBs, although only traces have been detected in tlic latter years Hie Tact that levels in these composites have declined to only tuiccs further suppon the inference that the meat, poultry and eggs no longer contain detectable PCBs and that the low level findings aic probably due to the fish in these composites. This would imply that the PCB levels in the diet may have "bottomed out" and may remain static until such time as there is a change in the PCB residues in fish Data compiled from studies sponsored by the National Marine Fisheries Service (N'MFS) (<5J) also suppoit the continuing presence of PCB res idues in fish. A compihuion of PCB daia. reptcsenting the results of all the mcasuicmcnts known to NMFS on PCBs in fish used in the U S. dial, indicates several important points: (1) while at one lime or another, some PCB mcasuicmcnts have been made on many fish, there is an inadequacy of information on PCB residues in the most-impoi rant fish items in the fish diet; (2) sampling and analysis have been sporadic and not designed to measure trends in human exposure: and (3) systematic sur veys of neither tlic important items nor the species most likely to be contaminated have been under taken. However, these survey data do show that, in gen eral, U. S. fish caters include a wide variety of fish items in (heir diet and that some 93% of the U. S. population (197 million) consume fish, with the av erage annual consumption of fish being If !b/yr per person. At ptcscnl, it is difficult to estimate all human exposure to PCB from eating fish, either from the population as a whole or subgroups at higher nsk of consuming large quantities of fish with higher PCB residues. Fiagmcntary evidence from NMFS data suggests that the exposure of the population as a whole from PCB residues in ingcsled fish is proba bly well below 19 pg/day per consumer, based on PCB levels which arc estimated to be below I ppm for 19 g of fish consumcd/day. This can be com pared to (he results of (he FDA Total Diet Study, where it has been estimated that the overall PCB daily intake is on the order of 5-10 pg'dny for the general population. The lower FDA estimate is based on the methodology of the Market Basket Survey where fish arc purchased at the consumer level and would not be applicable to diets which include a high consumption of fish from certain areas with high PCB residues. A recently completed study (33) has attempted to assess some of the consequences of human expo sure to PCBs from the high consumption of fish from contaminated areas. The results of tliis study show that a group ol sports fishermen consumed an average of 24-25 lb of fish/pcrson/ycar. with the highest individual exposure for a 2-year period re pented as ISO Ib/yr PCB residues in cooked fish ranged Horn 0.36 to 5.38 ppnt. Although there w.is a wide lange of blood PCB levels for cadi quantity uf fish consumed, ihcrc was a highly significant cor relation between the reported quantity of Lake Michigan fish consumed and the concentration of PCli in the blood of study p.niicip.ints, with the higher icportcd fish consumption being associated wuh higher PCB blood levels The blood values ranged fiont a low of 0 007 ppm in the control group (fish consumption less ihan 6 Ib'ycar) io a high of 0 366 ppm in the exposed gioup (fish consumphon 24-25 Ib/ycar) These invcstigaiors calculated that the amount of PCB ingested by the exposed group could average 46.5 mc'ycnr and ranged from 14,17 to 114.31 mg/ year. While no systematic adverse health effects could be demonstrated tn the exposed group when compared to controls, the investigators caution that any long-term chronic cTfects arc unknown at the present time Additionally, it can be concluded that exposure similar to those reported in this special group will continue and there is the likelihood that as sportsfishing becomes more popular, larger numbers of people may be exposed in a similar way. Although human exposure to PCBs fiom air and water is probably minimal, there seems little ques tion that such exposure docs occur Samples oT am bient air collected in Florida. Mississippi and Col orado. show that PCBs were present at all loca tions. The average concentration at each of the thiec locations was approximately 100 ng/m1 of air. Studies of surface water from the major drainage basins of the United Suites report the widespread occurrence of PCBs in both surface water and bot tom sediments. Mean tcsiduc levels of PCBs m the surface water ranged from 0.01 to 0.05 ng/S., with a maximum residue level of 20.0 ng/[. In Wisconsin, effluents from cooling water in aluminum foundries contained PCBs ranging from 11.5 to 335 ppb. Effluents from paper mills tanged from 0.01 to 25 ppb. Analysis of snow melt water from Wisconsin cities showed PCB residue levels of 0 17 to 0.24 ppb, suggesting thai fallout of PCBs from the air may be an important source of PCBs entering the waters of the state. In Michigan, testing of 900 samples of industrial effluents showed 22% had PCB residues >05 pg/1.. 8% > 1.0 pg/1., 6% > 10 fig/L. and 2% > 100 pg/l. With sludge disposal taking place by incineration, landfill and crop or pasture application, the con tinuation of PCBs in the environment seems obvi ous. Adverse human health effects resulting fiom PCB June 1978 195 HONS 206405 T exposure have come primarily from studies of oc cupational cxposuie and from human exposure through the ingestion of contaminated rice oil in Japan, Schwartz (6-1) provided some of the earliest re ports of rtdscr.sc hcnlrii effects due to occupational exposure in the U, S. in which he described skin lesions and symptoms of systematic poisoning among workers who were reported to have inhaled chlorodiphcnyls There have been numerous re ports over the ensuing years describing cutaneous eruptions and of systematic manifestations as well, among marine electricians, machinists, capacitor and tiansformcr manufacturing workers, and others occupationally exposed to PCBs. The skin lesions described by Schwartz (6-0 in 1936 have come to be designated as "chloiacnc." Part of the chloracnc lesion resembles adolescent acne, but is generally more severe and the lesion distribution is inconsis tent with adolescent acne, Hara (65) and Husegawa ct ai. (66), have reported dermatologic ailments which include "brown chromodermatosts'1 of the dorsal joints of the hands and purple eruptions of the face and neck. How ever, Hasegawa et al. (66) performed a health sur vey of workers in carbonless copy paper factories, (wo years after the use of PCD in such processes had ceased, and reported no derma! effects nor liver function, urine or blood test abnormalities. PCB blood levels were reported as 0.01-0.02 ppm. Typical clinical findings in the human exposure to PCB which occurred in Japan in 1968, and which resulted from the ingestion of rice oil contaminated with Kanccblor 400 included chloracnc and in creased pigmentation of the skin, increased eye dis charge, transient visual disturbances, feeling of weakness, numbness in limbs and some disturbance in liver function. Adult Yusho patients had pro tracted clinical disease with a slow regression of syroploms and signs. In the dose-response epidemiologic study, the average cumulative intake of PCBs leading to oven symptoms was 2,000 mg, with the lowest dose leading to overt symptoms being 500 mg. However, Kurnlsunc ct al. (67) have introduced a new factor into the Yusho Incidence with the finding thal the ticc oil contained cWormalcd dibenzofurans (Cl-DBIr) at 5 ppnt. Nagnynmn cl al. (65) report that the toxicity of (Cl-DBF) is said lobe from 200 to 500 times that of PCD. Whether or not the (Cl-DBF) contaminant is the crucial toxic substance produc ing the symptoms observed in the Yusho incident, or whether the exposure to the high levels of Knncchlor 400 produced the observed effects, or whether there was an interactive process taking phcc is unknown. The data necessary for determining reasonably accurate time and dose exposme to PUB in indi viduals in Michigan is either unavailable or nonexistent. Attempts to secure accurate dietary intake with the PBB levels in food and the duration of consumption have been unsuccessful. It is hoped that data to be received front the Michigan Depart ment of Public Health may provide sonic basis for crude estimates. While there appears to be no evidence at the mo ment to indicate acute health effects from exposure to PBB, any chronic effects remain largclv un known, A large-scale epidemiological study is ex pected to get undei way shortly to identify all the farm famdy members front quarantined farms, a large group of study subjects secondarily exposed to PBB through the purchase of farnt pioducts on a regular basis from quarantined farms and a control group of individuals not exposed to PBB contami nation. This study will continue efforts to identify any acute or chronic effects of PBB exposure through physical examination, biochemistry tests, and dietary histones. Efforts will continue to assess the original FireMaster BP-6 for the presence, if any. of chemical contaminants which might present human health hazards. In the meantime, a tenfold safety factor for PBBs when compared to PCBs ap pears both reasonable and acceptable based on all currently available scientific data. Much vvotk remains to be done concerning the toxicity of PCBs and PBBs and the association of these compounds with any demonstrable adverse human health effects. REFERENCES I Hutiinpcr. O.. Safe. S.. and Zrtfco. V. The Chemistry of PCBs. CRC Pres*. Cleveland. 1974. 2. Crosby. D B.. and Moilanen. K. W. Photodecomposilion of chlorinated biphenyls' upd jjiitcniofurjn*. Bull. Environ. Contain. Toxicol. 10: >72 (|V7. }, Zilko, V., Mulzinpcr. O .and Choi. P. M. K. Contamination of ihe Bay of Fund)-Gulf of Maine area with PCBs. PCTs. chlorinated DBF, and DDU. Environ. Ilcalih Perspcct. I. 47 (19721. 4. Vcilh, G. D. Baseline concentrations or polychlorinated biphenvls and DDT in kale Michigan Fish, 1971 Pevtic. Monitoring J, 9: 21 (19751. 3. Sissons. D.. and Welti, D. Structural idrnlinciilinn of polychlorinated biphenvls in commercial mixture by eistiquid chrommopr.iphi. nuclear magnetic resonance and mass spedrometry. J ChronWtogr. Ml l,'(l97ti 6, McKmnev, J, D , ct al. 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