Document 3NV5oNMaBmoDGa4XnmeovJ61D

KOTICEr This material ra^ bo proteotod by copyright Environmental Health I'erxpeetives Yol. 24. pp. 191-198. 1978 General Su Emm airy and Conclusions 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 in the environment mainly based on laboratory studies. The known resistance of aryl chlorides to chemi cal oxidation and hydrolysis presumably was a major factor in the promotion of PCBs for industrial uses. Exposure to nonmetabolic 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 sunlight-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 reductive dechlorination to biphenyls of lower chlorine con tent is a predominant alteration route although for- * Members of the Subcommittee: A. C. Kolbye (Chairman), Food and Drug Administration, 200 C St., S. W.. Washington, D. C. 20204; J. L. Buckley; J. Burke, F. Cordlc; P. Corncliussen; D. Firestone; L. Fishbcin; G. Flamm; G. F. Fries; A. Gardner; L. Garlhoff; H. Gcrstner; J. A. Goldstein; I). Hacklcy; C. F. Jclinck; L. Kasza: R. Kimbrough: T. E. Kopp: Y. Ku; R. L. Lehman; W. Marcus: H. B. Matthews: J. D. McKinney: J. McLaughlin: J. A. Moore; 1. I. Pomcrantz; R. A. Rhoden: J. A. Roach; S. Shibko: R. E. Shapiro: R. H. Teske; and W. Trotter. mation of more polar compounds, including a chlorinated dibenzofuran. has also been reported (/, 2). The diverse conditions of the environment make it difficult to predict accurately the end products and rales of photoalteration of chlorinated biphenyls. From a comparison of carbon-halogen bond energies, brominated biphenyls might be ex pected to be more readily altered by light than chlorobiphenyls. But because of the lower volatility and different end uses of bromobiphenyls, 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 (.?, 4). Considering the major com ponents of Aroclor 1254 (5), it appears that penta-, hexa-. and heptachlorinated 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 chlorine sub stitution pattern. Individual chlorinated biphenyls are now quite accessible through synthesis and re cent studies have begun to obtain these types of biological data. 1 Studies with the use of a group of five symmetri cal hexachlorobiphcnyl isomers in chicks (6) and in mice (7) indicated that distinct difference in toxicity are possible and these differences could be related to structure. The isomers with chlorine substituents in the 4,4' positions appeared to accumulate more rapidly in adipose tissue and showed increased ac tivity in the liver and greater overall toxicity 5. S). Comparison of two pentachlorobiphenyls in laying chicks again indicated the one isomer with 4,4'- substilution to have greater toxic effects (9, 10). Structure-activity relationships, particularly for biphenyls known to be major components of com mercial PCB mixtures, could be useful in assessing the potential hazard of these compounds. June 1978 191 DSW 378433 i i i )i iII \{ i 1 STLCOPCB4099795 A major part of determining human exposure to A range of Cl-DBFs (from dichloro through PCB residues in foods is evaluating the adequacy of hexachloro) have been reported in various Aroclors the analytical methodology used and the signifi (15: 16) and two specific compounds, the 2,3,7,S- cance of the data obtained. The methods applicable tetrachloro- and 2.3,4,7,8-pcntachlorodibenzo- to PCB determination are complex and to be judged furans, have been identified (/7). Quantitation of ^adequate should give acceptably reproducible re Cl-DBF contaminants in PCB mixtures, a difficult sults in the hands of experienced analysts. The de procedure, suggests total Cl-DBF levels in the low gree of success of intcrlaboratory collaborative parts per million range (16, IS). The presence of studies helps measure the adequacy of a method. Cl-DBF in a synthesized, individual, symmetrical PCB residues arc multicomponent mixtures. chlorinated biphenyl has been reported (19). Many common chlorinated pesticides are extracted Chemical analysis of these individual from samples along with the PCBs. Procedures for chlorobiphenyls may be necessary prior to their use separation of PCB residues from interfering pes in toxicological and other biological studies. ticides thercforc'become important as a prerequisite There have been no published positive findings of to quantitation. Several different quantitation tech Cl-DBFs in environmental samples or in foods other niques have been used (/). Comparison of PCB than rice oil. The finding of Cl-DBFs in such sam residue data is difficult where standardization of the ples would not necessarily implicate commercial quantitation procedure is lacking. PCBs as the source of these contaminants, since It has been shown that recovery of PCB mixtures Cl-DBFs (generally the higher chlorine levels) have purposely added to food samples, using commonly `been reported in other industrial chemicals (20-22). applied analytical methodology, varies with the av It 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 {II). Analytical procedures for determination of PCB and PBB (the latter is predominantly a hexabromobiphenyl) residues are essentially similar. Metabolism and Biochemical They differ somewhat in cleanup of the extract and in the use of a higher column temperature for gas Toxicity chromatographic 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 are known to alter. On a molar ministration methodology. For PBB residues, the basis, the PBBs are approximately fivefold more limit of.quantitation is approximately 0.05 ppm in potent than the PCBs in inducing increased levels of fats and 0.01 ppm in nonfatty foods. Interlaboratory the MFO enzymes (23). 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 thepara > ortho The chlorinated dibenzofurans (Cl-DBFs) have >.meta positions respectively (24). 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-tetra- MFO inducers in that they induce the formation of chlorodibenzo-p-dioxin and the similarity in struc both Type I and Type II P-450 (25), but this induc ture between dibenzo-p-dioxin and dibenzofuran tion may have been due to the fact that the commer (12) and from the few toxicity data that have been cial formulation used in the study was a mixture of published for Cl-DBFs (13). Recent data indicated twenty or more PCBs which were metabolized to an the toxicity of 2,3,7,8-letrachIorodibenzofuran ap even greater number'of metabolites. In addition, proaches that of the analogous dibenzo-p-dioxin. at many, if not most commercial PCB formulations least in chicks and in guinea pigs (14). If the chlori contain trace amounts of chlorinated dibenzofurans nated dibenzo-p-dioxins can serve as an example, (26). These compounds may be up to 170 times chlorinated dibenzofuran toxicity can be expected more potent as MFO inducers than the PCBs. The to vary with number and position of chlorine atoms chlorinated dibenzofuran concentration of Ameri on the parent ring system. Relationships between can PCB formulations is usually quite low when structure and toxicity will emerge as more Cl-DBFs they arc produced: however, the effect of long-term are synthesized and tested for toxicity. exposure is unknown, in any case, since induction 192 Environmental Health Perspectives I t I ft ft i I t i i * DSW 378434 of the MFO enzymes may result in increased hor varies greatly and often ultimately determines the mone metabolism or carcinogen activation, expo toxicity, mutagenicity, or carcinogenicity of the sure to the PCBs and PBBs should be limited on parent compound (39), the PCBs offer such a range that basis alone. of degree and position of substitution that it would PCBs and PBBs administered arc relatively high not be unlikely to find that one or more of these concentrations, usually 50 ppm or higher in the diet, PCB metabolites would have the proper stability to to laboratory animals have been shown to cause be a mutagen or a carcinogen. Thus a move from the porphyria (27), disfunction of the thyroid (25), inhi more highly chlorinated PCB formulations to the bition of various enzymes (29), changes in the liver less chlorinated ones may help solve the long-term to body weight ratios {30), various disorders of the residue problem only to intensify other problems. liver (31), and to alter the level or utilization of cor ticosteroids (32), and vitamins A, D, and E (33-35). Animal Toxicology Certain of the less chlorinated PCBs have also been shown to have a mild estrogenic effect when tested Gleaning the information that is now available on in the immature rat and mouse (36, 37). Howevefr animal toxicology makes it obvious that different most of these parameters have not been studied in commercial mixtures of PCBs elicit different toxic sensitive species or demonstrated at low exposure responses in animals, and that different animal levels in laboratory animals. species vary in their susceptibility to the toxic ef The available data imply that the PCBs and PBBs fects of PCBs. Reproduction is severely affected in containing six or fewer halogen atoms are readily mink at a dietary level of 5 ppm Aroclor 1254, and a absorbed from the gut of higher animals.'The avail slight effect is still noted at a dietary level of 1 ppm able data also imply that the PCBs are not excreted (40). In rhesus monkeys, reproduction was reduced to an appreciable extent prior to metabolism to at a dietary level of 2.5 ppm of Aroclor. 1248 (41). In more polar compounds, and that long-term PCB rats a dietary level of 20 ppm Aroclor 1254 de storage is in the skin and adipose tissue (38). Studies pressed reproduction, while in the same rat strain of PBB metabolism are not yet available. Since tis (Sherman), in a study conducted simultaneously in sue samples from birds and mammals with known the same laboratory, a dietary level of 500 ppm exposures to PCBs usually contain only those PCBs Aroclor 1260 was necessary to reduce reproduction with five or more chlorine atoms, it is assumed that (42). In comparative studies done with European the less chlorinated PCBs have been metabolized products, Phenoclor DB6 and Clophen A60, and the and excreted. On the other hand, there is little evi American product, Aroclor 1260, the European dence that fish can metabolize any PCB, and an products were more toxic to chickens than the analysis of fish tissue usually shows a PCB pattern American product (43). The difference in toxicity in very similar to that to which the fish were exposed this study was attributed to contamination of the (//). European products with chlorinated dibenzofurans Laboratory studies have demonstrated that the and perhaps chlorinated naphthalenes. However, if rate of PCB metabolism and thus excretion is ap the differences in the effect on reproduction by the proximately inversely proportional to the degree of different Aroclors are compared, the con`amination PCB chlorination so long as thme are two adjacent with chlorinated dibenzofurans may not be the deci unsubstituted carbon atoms on the biphenyl sive factor. molecule. When two adjacent unsubstituted carbon Hepatic porphyria has been produced in a atoms are not present the biological half-life of the number of species, namely the chicken, rabbit, given PCB may be a matter of years and accumula Japanese quail and rat, by a number of commercial tion of high tissue concentrations with continued mixtures, such as Clophen A60, Phenoclor DP6. and exposure is inevitable (55). It should be noted that Aroclors 1016, 1242, 1254, and 1260 (27. 43-46). the major constituent of FireMaster BP-6 does not Hepatic porphyria has not been reported in the have two adjacent unsubstituted carbon atoms and monkey, mink, or human, which are species quite that the corresponding PCB has been shown to have susceptible to the toxic effects of PCBs in other an extremely long half-life in the laboratory rat and ways. Aroclor 1254 and Aroclor 1242 produced he probably the human population as well. . patic porphyria in the female rat at doses lower than It should also be noted that metabolism can also Aroclor 1016. Again, different commercial mixtures result in further complications of the PCB problem, produce this toxic effect at different dosage levels. because those PCBs which arc most readily The hepatic porphyria occurs concomitantly with metabolized and excreted arc those which are most an increase in ALA synthetase in the liver. Mixed likely to be metabolized via arene oxide inter function oxidases are also induced in the liver and mediates. Whereas the reactivity of arene oxides comparative studies with PCB isomers have June 1978 .* 193 >** T* V? dS\N 378435 STLCOPCB4099797 suggested that if the 4,4' positions on the biphenyl ring are occupied by chlorine atoms the effect is most pronounced (47). The liver is the primary target organ for PCBs in the rat. Early changes include hepatomegaly, with a concomitant increase in smooth endoplasmic re ticulum, lipid accumulation at higher dietary levels (20 ppmfor Aroclor 1254 and 1260). and ultrastructural changes such as atypical mitochondria and the formation of "fingerprints'' (concentrically ar ranged membranes surrounding lipid vacuoles) in the hepatic cytoplasm. An increase in mitotic fig ures and cell breakdown are increasingly noted with either higher doses or longer exposure (48). These changes are not as pronounced with Aroclor 1242 or 1016. Similar changes have been reported in the primate (41). In the mouse, liver tumors have been produced with Aroclor 1254 (49) and Kanecldor 500 (50) and in the rat with Kancch!or400 (5/) and Aroclor 1260: Some tumors have also been produced with Aroclor 1242, 1254, and 1260 (52) in rats in a separate study. In one study with Aroclor 1260, some of the tumors were classified as hepatocel'ular carcinomas (31). 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 very high for subgroups with a high intake of fish from polluted waterways or in some occupational situations. This is emphasized by the fact that the dietary levels which produce tumors and the rela tively low dietary levels which affect reproduction (2.5 ppm in the monkey and 1 ppm in the mink) of some commercial PCB mixtures do not represent a no-effect level. It is presently not known what the no-effect levels are. 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 dibenzofurans. ' In the primate, in addition to the effect on the liver, the gastric mucosa (5.?), the skin, and the Meibomian glands are 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 hexachlorobiphenyl isomers demonstrated that the 3,4,5,3',4',5'-hexachIorobiphenyl was the most toxic while 2,3,6,2',3',6'-he.\achIorobiphenyl was the least toxic isomer (7). Pcntn-, hexa-, and heptachlorobiphcnyls arc preferentially retained in mammalian adipose tissue for extremely long periods of lime (48) at fairly high concentrations in the rat fora recovery 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 chlorinated naphthalenes arc toxic within the same dosage range as the chlorinated biphenyls, the chlorinated dibenzofurans probably have a greater toxicity. It is assumed that 2,3.7,8tetrachlorodibenzofuran is the most toxic of this group of compounds. This compound also shows marked species variation. While the single oral LDr,,, in guinea pigs is between 5 and 10 /ag/kg body weight, 1000 /xg/kg TCDF given orally had no effect on rats. Mice arc equally insensitive to the toxic effects of TCDF (14). For the brominated biphenyls, limited toxicity data are only available on mixtures containing pre dominantly hexa- and octabromobiphenyl. Both mixtures differ sufficiently in isomeric composition so that their toxic effects may quantitatively be quite different and also different from the PCBs. Again, the problem of toxic 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 low-level exposure should result in measurable toxicity. Additional animal studies are needed to resolve some of these problems. Poor metabolism and excretion of the brominated biphenyls may lead to long retention of these com pounds predominantly in adipose tissue with ac cumulation to very high levels on continued expo sure. Whether this would lead to sufficient recircu lation of the chemicals to cause toxic effects on target organs is presently not known. Human Exposure Several reports (54-61) provide evidence that would indicate that a substantial proportion of the population of the United States has been exposed to PCBs. Minimal human exposure of the population to PCBs has occurred from food, air and water, while significant human exposure appears to be limited to sports fishermen consuming fresh water fish from contaminated streams and lakes, and to occupational exposure in industrial workers. Jclinek and Corneliusscn (54), in reviewing data from the FDA Total Diet Study (62). report that all food classes of the total diet declined to no PCB occurrences except.in these meat-fish-poullry com posites. About 40% of these composites continue to 194 Environmental Health Perspectives DSW 378436 i > i I t r t STLCOPCB4099798 contain detectable residues of PCBs, although only traces have been detected in the latter years. The fact that levels in these composites have declined to only traces further support the inference that the meat, poultry and eggs no longer contain detectable PCBs and that the low level findings are 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 (NMFS) (63) also support the continuing presence of PCB res idues in fish. A compilation of PCB data, repre senting the results of all the measurements known to NMFS on PCBs in fish used in the U. S. diet, indicates several important points: (1) while at one time or another, some PCB measurements have been made on many fish, there is an inadequacy of information on PCB residues in the most-important 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 the 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 eaters include a wide variety of fish items in their diet and that some 93% of the U. S. - population (197 million) consume fish, with the av erage annual consumption of fish being 15 lb/yr per person. At present, it is difficult to estimate all human ' exposure to PCB from eating fish, either from the population as a whole or subgroups at higher risk of consuming large quantities of fish with higher PCB residues. Fragmentary evidence from NMFS data suggests that the exposure of the population as a whole from PCB residues in ingested fish is proba bly well below 19 /xg/day per consumer, based on PCB levels which are estimated to be below 1 ppm for 19 g of fish consumed/day. This can be com pared to the results of the FDA Total Diet Study, where it has been estimated that the overall PCB daily intake is on the order of 5-10 /xg/day for the general population. The lower FDA estimate is based on the methodology of the Market Basket Survey where fish are 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 (55) 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 this study show that a group of sports fishermen consumed an average of 24-25 lb of fish/pcrson/ycar. with the highest individual exposure for a 2-ycar period re ported as 180 lb/yr. PCB residues in cooked fish ranged from 0.36 to 5.38 ppm. Although there was a wide range of blood PCB levels for each quantity of fish consumed, there was a highly significant cor relation between the reported quantity of Lake ' Michigan fish consumed and the concentration of PCB in the blood of study participants, with the higher reported fish consumption being associated with higher PCB. blood levels. The blood values ranged from a low of 0.007 ppm in the control group (fish consumption less than 6 lb/year) to a high of 0.366 ppm in the exposed group (fish consumption 24-25 Ib/'year). These investigators calculated that the amount of PCB ingested by the exposed group could average 46.5 ma'year and ranged from 14.17 to 114.31 mg/ . year. While no systematic adverse health effects could be demonstrated in the exposed group when compared to controls, the investigators caution that any long-term chronic effects are 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 from air and water is probably minimal, there seems little ques tion that such exposure docs occur. Samples of 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 three locations was approximately 100 ng/m3 of air. Studies of surface water from the major drainage basins of the United States report the widespread occurrence of PCBs in both surface water and bot tom sediments. Mean residue levels of PCBs in the surface water ranged from 0.01 to 0.05 jxg/1., with a maximum residue level of 20.0 /xg/1. In Wisconsin, effluents from cooling water in aluminum foundries contained PCBs ranging from 11.5 to 335 ppb. Effluents from paper mills ranged 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 that 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 > 0.5 /xg/1., 8% > 1.0 /xg/1., 6% > 10 /xg/1., and 2% > 100 /xg/1. 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 from PCB June 1978 . 195 DSW 378437 yM STLCOPCB4099799 I exposure have come primarily from studies of oc cupational exposure and from human exposure through the ingestion of contaminated rice oil in Japan. Schwartz (64) provided some of the earliest re ports of adverse health 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 transformer manufacturing workers, and others occupationally exposed to PCBs. The skin lesions described by Schwartz (64) in 1936 have come to be designated as "chloracne." Part of the chloracne lesion resembles adolescent acne, but is generally more severe and the lesion distribution is inconsis tent with adolescent acne. Hara (65) and Hasegawa ct al. (66), have reported dermatologic ailments which include "brown chromodermatosis" 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, two years after the use of PCB in such processes had ceased, and reported no dermal effects nor liver function, urine or blood test abnormalities. PCB blood levels were reported as 0.01-.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 Kanechlor 400 included chloracne 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 symptoms and signs. In the dose-response epidemiologic study, the average cumulative intake of PCBs leading to overt symptoms was 2.000 mg, with the lowest dose leading to overt symptoms being 500 mg. However, Kuratsune et al. (67) have introduced a new factor into the Yusho incidence with the finding that the rice oil contained chlorinated dibenzofurans (Cl-DBF) at 5 ppm. N'agayama ct al. (65) report that the toxicity of (Cl-DBF) is said to be from 200 to 500 times that of PCB. 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 Kanechlor 400 produced the observed effects, or whether there was an interactive process taking place is unknown. The data necessary for determining reasonably accurate time and dose exposure to PBB in indi viduals in Michigan is cither 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 from the Michigan Depart ment of Public Health may provide some 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 largely un known. A large-scale epidemiological study is ex pected to get underway shortly to identify all the farm family members front quarantined farms: a large group of study subjects secondarily exposed to PBB through the purchase of farm products 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 histories. 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 work remains to be done concerning the toxicity of PCBs and PBBs and the association of these compounds with any demonstrable adverse human health effects. 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Pharmacol. 36: 65 (1976). 7. Biocca. M. Toxicology of selected symmetrical hcxachlorobiphcnyls. Biological responses in chickens and mice. Paper presented at National Conference on Polychlorinated Biphenyls. Chicago. 1975. 196 Environmental Health Perspectives i i i t i f t l I I I 1 t V ) t * DSW 378438 i-- TT- STLCOPCB4099800 8. McKinney. J. D. Toxicology of selected symmetrical licxa- chlorobiphenyl isomers: Correlating biological effects with chemical structure. Taper presented at National Conference of Polychlorinated Biphenyls. Chicago. 1975. 9. Ax. R. L.. and Hansen. L. G. Effects of purified PCB analogs on chicken reproduction. Poultry Sci. 54: 895 (1975). 10. Ax. R. L., Miller, W. L.. and Hansen. L. G. Toxicity com parisons of two pentachlorobiphenyls. Paper presented at American Society of Animal Science. Midwestern Section. 1976. 11. Stalling. D. 1... and Mayer. F. L., Jr. Toxicides ofPCBs to fish and environmental residues. Environ. Health Perspect. 1: 159(1972). 12. 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