Document 65vQYJ0JoVxo0VOERLJRn4k0R

rCB's AND THEIR ENVIRONMENTAL EFFECTS Author D. 0. Peakall Canadian Wildlife Service Ottawa. Canada Re If fee: K W. Hiifhrnit|li hodepn far M*rlnr Lthurtlory HodatB )Ly, j \ 1. INTRODUCTION Hutxingcr et al. recently reviewed <hc chemistry of PCB't. In Iheir preface these authors state, "Opinions on (he importance of these ubiquitous ly distributed industrial compounds, however, still vary (ready. The authors do not wish to enter Ibis discussion." In this ariicle, an attempt is made to assess the biological impact of these materials, both on man and other creatures that Inhabit (his planet The information tin the production and usages of these materials is briefly reviewed, followed by a more detailed look ai levels found in various types of orpnisms in various parts of the world. This information is used to consider the routes and rates of transfer of these materials through the ecosystem and (heir biological mag nification during these processes. The physio logical effects of PCB's ire then considered, and their likely importance is assessed by comparison with existing environmental levels. The picture it complicated by the fact that we are not dealing with a single compound. The basic structure of PCB's is: XX XX OO* XX XX where any of the positions marked with x can be substituted by chlorine. The physical properties of PCB's have been described in detail elsewhere.1 In brief. Ihey are chemically inerl. are noi hydro lysed by water, and resist alkalies, acids, and olher corrosive chemicals They have low volaiilily, their boiling points ranging from 278C for Aroclor 1221 to 415^ for Aroclor I268.1 All arc stable to prolonged heating al IS0*C. The solubility of PCB's in water is very low, and is high in hydrocarbon solvents The degree of chlorination is expressed by the number following (he trade names. Fur (he Aroclor series ihe last two digiis give ihe percentage of chlorine. The Japanese and American equivalents are given in Table I. 2. PRODUCTION OF PCB'S Detailed figures on produclion and usages of PCU are only available for ihe U.S. (Table 2) and Japan (Table 3). Additionally, PCB's are known to be manufactured in Germany (Bayer). France (f.odelec), Italy (Caffaro), U.S.S.R. (Sovol) and v'zechoslnvikia (Chemko), although production figures are not available.* In 1970 Ihe combined production of Japan and ihe U.S. was 107 million pounds, and (he total world production can he estimated at ISO to 200 million pounds. This is Seplcmbet I97J 4*9 TABLE 2 TAULt; 1 ArtierH'tn trade name Aruclor 12 32 Aroclor 1242 Aroclur 124X Anrclor 1254 Aroclor 1260 Jalxmau' tia<U name Knnci'liiui 2(JU 300 -400 J00 -600 t (`liluime 32 42 48 54 60 tvmiMinvni* Ok Irn M*nn,iKd ti'liatitlitritiailfU pt'nuthliuiiMii'd Ikaui hlmifMtCil probably half the maximum production of DDT that occurred in the late I960*. The figure* in Tabic 2 relied Ihe rest rid inns placed on the usages of PCB's by Monsunlo. and currently PCB's are told only to Ihe electrical industry for use in closed systems as a dielectric fluid in transformers and capacitors. 3 TRANSPORT OF PCB'S IN THE ENVIRONMENT The basic document for this section is the analysis made by Nisbct and Sarofnn,' although an attempt is made to update in the light of more recent research and the restrictions placed on the usage of PCB's. These workers made the following assumptions on the useful ttfe of objects contain ing PCB's: A. The rate at which capacitors arc dis carded, primarily into landfill dumps, is equal to half the rate of production. B- Ten percent of tales of transformer fluid is to replace scrapped oil. C. The rale of vaporization of plasticizer amounts to 101 o 20% of sales. D. The rate of disposal of plasticizer* into dumps is equal to the residual 80 to 90% of sales. Using these assumptions Nisbct and Sarofitn cal culated grots estimate* of the rates of input and accumulation of PCB's in North America in 1970 (Table 4). Starling in 1970. rennet him were placed by Monsanto (the sole US producer) to reduce Ihe environmental input of PCB's. The use of PCB's in pesticide formulations was dir con tinued in early 1970 although evidence t ggests that this was a minor use Later in 1970, sales of PCB's fur plasticizers, surface coalings, and adhesives were stopped. The main uses noware in sealed electrical transformers and capacitors and in heat tiansfei systems. Monsanto has made arrange- moots In destroy spent PHI fluid and destroyed 2.2 X 10* metric Ions in 1973 and 1.2 X 10' tnclric tons in |*)74* On ihe basis of ihese changes in use pultons, the inputs and aecmitula1 inns have been recalculated for l`74 (Table 4). Surer PCB's have not been used as plasticizers I'm three years, the input from the vaporization from this source should now be negligible. Valorization form open burning is dependent on Ihe amount of PCB's reaching the site, and it is arbitrarily assumed that this is decreasing *i a rate of 20% pci year. Ntshci and Surofim' estimated that 1.5 to 2 X 111' metric ions per year of PCB's were vaporized into the atmosphere in 1970 Now it is likely that Ihe a mourn has decreased by an otder nf magni tude since the mainr source, vaporization from plasticizers, Inis been removed. Mauglt* reported ott the possibility that PCB's could be formed Irons DDT under the influence of UV light, it was pointed out earlier* that this would only he expected to lead to dk'hlmobipitcuyh which are riot normally found in environ mental systems, Nisbcl artd Sarotiin' calculated that the total input of PCB's into the seas around North America, mainly into the Atlantic, has been I.SX ID* tons This figure can he compared to the global value calculated for DDT of S X 10s torts ' On an annual basis, the fluxes into the North Atlantic would he 5 X Its' tons fur PCB's and 25 X 10' tons For DDT. Using the latter figure, the SCtPfSlndy of Critical liuvirniimeLilal Problems) calculates a figure of 5 ng/l for DDT it* lire suifact mixed layer assuming a residence time ni 5 years These calculations are hased on (he ptoduclitm and usage pattern* of the late 1960s, and in North America these have changed considerably in the Iasi 5 years. Scba and Corcoran* measured levels of organochlorntc pesticides in surface slicks and sea water in 1968. They found values ranging from 470 CJtC Crtrieal R rvirwl nr Hmironmcmtl Control mons 206846 Si TABLE 2 rCB hetaiitii end Unp in dx U-S. (Metric Tom) 19ST Dometbc u*e by cat<p>i) Heat transfer - HydrauHcs/lubricantt 806 Miwtlaneour Indus! rial 332 Ttarafomer 6.471 Capacitor flmkinr 8.5M applications . Pvtroievra additive* - 1931 - 773 378 2.139 7.030 1,969 1939 - 1.342 704 2.992 8.250 2,286 I960 1961 1,262 779 3.960 1,413 3722 - 2.055 1.057 3.147 7.961 4.549 1962 71 1.957 147 3992 7.691 4.462 1963 291 1.973 764 3645 7.103 4.590 1964 1965 1966 1967 1961 1969 1970 1971 1972 1973 1 464 3117 846 3991 9.770 3.168 611 2.308 920 4.321 11.174 5.848 M3 2.129 <89 4.455 14.442 6.740 1.131 2.322 713 5.535 14.151 6.680 1.264 2.113 642 5.792 14.775 7,202 1.525 4.020 540 6.052 12.511 1230 1.979 3.701 113 6.914 13354 9,761 _ _ __ _ 719 1.530 776 577 5.567 7,070 1.630 376 _ 12.828 - - 18.17 - _ Domeroc me by FCI grade Arodor 1721 11 Aroctor 1232 91 Aroctor 1242 9,111 Aroctor 1241 8<9 Aroclor 1234 2.230 Afoclot 1260 3,793 Aroclor 1262 76 Aroclor 1261 - Aroctor 1016 - Production * 1 57 5.222 1.279 3345 2.997 92 36 - * 127 120 6.799 1.692 3377 3370 179 31 52 77 9.091 t.414 3044 3,665 163 94 * 47 120 9.973 2.072 3.147 3270 110 79 70 112 10.327 1.7 31 3162 3,297 276 103 - III 6 9.255 2.506 2.955 3113 207 142 - 291 6 11.785 2.619 3740 4.267 223 95 - 115 4 15.762 2712 3.864 2915 279 98 - 264 1 19,771 2.507 3.517 2.937 384 142 - 221 12 21.527 2.352 3.341 3.208 420 144 - cl 45 22.427 2447 4.445 2626 360 140 - 254 136 22.745 2.125 4.911 2,220 356 150 - 738 130 24.294 2.036 6.210 2,445 512 165 - 1.107 <5 10.990 106 2.330 <64 1 - 1,667 15 - 364 404 1.747 152 - - 10.451 IB 3.100 . 3.988 - 11.765 16.960 11.237 19,176 22.367 25,416 30.240 32.924 37.654 62427 31.194 42,527 17,497 19.300 21.019 Domestic ulei 116.149 13.030 15,633 17.604 11.769 19.021 19.066 22.434 25.191 29,539 31.233 32,551 33597 36,530 17.150 13.204 18.87 1 Export t.123 2.041 2117 3.426 4.062 5.615 5.312 6.125 - 3.194 4.173 Produnion rifutn and plasikuer applications fWures available durinp year indicated **||.S export tales figures unavailable during year indicated nous 2Q*B*9 September 1971 47) f 472 CMC C n tw f TABLE 3 KB Piadactioa arf in )ap (Meartc Tom) Dometts w by dgtiir Elactncil ipparatv* Hen tvamnnttt Copy paper Other ina rrorfaction Imports Export* 1957 760 1951 7*0 1959 1,060 1960 1.320 1961 l,B60 1962 1.6*0 1963 1.270 196* 1.920 1965 1.990 1966 19*7 2.600 2.370 i960 1969 2.830 4.220 --to 1--00 30 40 120 170 ISO 2*0 10 2*0 400 450 660 730 720 1.290 30 100 no 300 390 780 1.320 to 150 ISO 200 no 210 240 270 270 260 3)0 820 910 1.260 1.6*0 2,220 2.190 I.SI0 2j*70 3,000 4.410 4,480 5.1)0 7,7)0 -- 60 100 110 -- - - - too 100 *0 160 500 720 540 590 Adapted from Faiiwara. K. fteporr. Department of Hygit*ic Chtmatry. 1Crota City 1 mutate. Kyoto )jp*n 197*. 1970 1971 5,960 *460 1.890 1.920 340 1.920 350 100 11.110 6.780 150 no 1.000 TJ0 in K u n n tn m n u o l Ctm trvf non$ 206050 TABLI. 4 litimilci o7 Hairs of Input and Accumulation of fCI'l in North America in (970* and 1974** (Metric Toni) 1970 1974 Vapnriraliun of plarriclreri Vaporiniion during open burning Lcaki anil dupmj of industrial fluidi Dcitioftd by incineration and open horning Dispnial in dumps and landfill! Accumulation in tervlee 1-2 * 10* 4 X 10' 4-5 X 10* 3x10* 18x10* 7 x 10* Negligible Mainly 1248 to 1260 I S X 10*7 4-J x 10*77 12 X 10*t 7 X 10' 4 x 10* *) loni Niahei, I. C. T. and Samfim. A. I'., tmwi*. Hftllh frrtpert., I, 21. 1972. `Calculaieil tiuin the attunipliimt of Niahei and Sitofim. aee text. - 7Aiuiming 207/year dectciac in fCH reaching open burning 77AtMimed to have decreated an order of magnitude. Partially due to cnlttelian by Montenin and parllally due to gieeier awataneaa and many fawet (lima handling the material. K0 ng/1 tome 25 miles off the Florida coast lo a maximum of I 2 7 |ig/l in Brscaync Bay No DDT compounds were delected in sea water, limit of detection was I ng/1. PCB's were not mentioned and presumably not examined Cm. Hartung and Klinglci* found that the pariiiioning coefficient for. p.p' DUT hclwcen nil and water is around I06. Finding thai ihe level in sea waicr was below i og/1 is noi surprising in view of the levels in oil dicks even though equilibrium may well nol be complete. The data in Table 4 confirm the low levels of DDT in the upper mixed layer, although by 1971 the usage of DDT had markedly declined in North America. Current evidence suggests that Ihe bulk of DDT transferred to the ocean is not dissolved in the upper mixed layer, nor is it present in aquatic organisms. It appears that DDT is aedimented, degraded beyond DDD or DDE. or co-dtstilled back into ihe atmosphere. At present there is tittle evidence on which lo evaluate the relative importaper of these mechanisms. The levels of PCB's are most interesting. The values for 1971 and 1972 (Table 5) are much higher thin would be predicted by calculation along the lines of the SCEP report. If one multiplies their value for DDT by ihe ratio of esitmaicd amounts of iransfei of PCB and DDT, one comes up with a figure of I ng/1 (5 ng/1 X ). Then the figures show a rapid IS x 10* decline to about I/30th ttf the earlier values. This shows that the levels in the upper mixed layer are in much more rapid equilibrium with atmospheric values than was previously indicated. In making these calculations one has to bear in mind that these measurements are cluse to the limit of analytical capability, and suggestions have been made'0 that many subsiancei as yet unidentified may be Included in the analysis and may introduce serious errors. The basic question is the accuracy nf these figures. While it is nol possible lo check the actual determinations, it is possible to cal culate the implications of accepting figures. If an area for the North Atlantic is 5.000 km1, then the volume of the upper mixed layer (100 m) would be 25 X 1010 ml. Assuming Harvey el at.'s value is 30 X 10~* * g/ml,1* then the amount in this layer of the North Atlantic would be 7.5 X 10** g or approximately 10s metric tons. This figure is high as compared with the calculuied annual flux to the lolat production of PCB's. The PCB found in tea water is of the 1254 pattern; the maximum annual usage of which is only 6 X 10'* metric tons. Even If higher Aroctors are included, the figure would be 10* metric ions. Thus. ih indications are that the determinations of Harvey et al are too high Bidleman and Olney11 show that the levels of PCB's In the surface microlayer (ISO pm) is September I97J 17) HONS 20665l .ji-y TABLES - fCB and DDT CMcrUtK>nf In North A Han Ik Surface Weters, 1971 |n 1974 Dale Aujuit 1971 July 1972 August 1972 September 1972 April 197) September 197) September 197) tebruary 1974 Mean KTl ng/l 25 41 )h )0 1 2 08 08 Mean 1)1)1 nfti n* <I <1 <1 <0 15 <1 *.*. IV* wm/prit Am'\ - <002 <0 0) <0 IS <0.5 - Irdomt Newfoundland Ncwitiiundtand Purlugat I'nMUFiil - Norwegian Sea Mauacliuu'lu - Hrrmuda Suryaisu Sea A/iuiu In Uorbadnt Sarftassn Sea New Ysnl Mew Lngljmt continental their Kelerenee Olncy and Outers cited In Harvey cl al . 197J 1 * Harvey tl al. 1971 '* Olncy and Ouinn. 1974 > tlarvry el al. 1974 " n.a. - not staled. t'hli'M'"' cnlis's 1 c it which O'1 ' l.nchi .1" Nagoya. tussling' higher I'', by |s>v'i" TtiC'-v Cults'Itl'M ' unptotatn tils' SICS'-1 dcts'sl 1*1 .111st 6.11. Likes s1' substantially htghct ihun subsurface water (30 cm). The surface, even in the absence of visible slicks, is an area of high content ration of oiganic materials '* The information 011 PCI) levels in sedimenls is confined to areas near sources of direct con lamina 1 coo Hmn el ai.15 made an analysis of PCD and DDE in a dated core from the Santa Barbara Basin of the coast of California. They found that PCB deposition stalled about 1945, and that (he rate of deposition in 1967 was 1.2X10'* g/m'/yeai. Holden1* and Halcrnw et al.1 * have found t'CD's in sludge and murine sediments near to dumping areas off ihe coasts of Great Bmafo. Linko et al.1* found residue levels of 0.01 ppm in sediments in the Baltic, and Dexter and Pavlou* 7 found residue levels* up to 0.7 ppm in sediments near Athens. An experiment of great interest would be to examine dated core samples from the North Atlantic remote from direct sources of contamination. Such measurements would enable us to balance the transport figures for both PCB's and DDT in the environment. The higher DDT/PCB ratios In the Pacific correlate with the findings of Bevenuc el al.1* who found DDT in all rain waler samples collected on Hawaii during 1971-1972 bul did not detect any PCB's. However, It should be pointed out that the sensitivity of PCB detection is considerably less thin for DDT. Bidienum and Olncy*1 measured the levels of PCB's and DDT in air, ihe surface microlayer. and subsurface water in the Sargasso Sea. The DDT/PCB ratios were low, typically 0.1 to 0.004. which is in line with the tow levels reported in /.ooplankton over a wide area of the North Atlantic.1 * which was cotisidctcd by Ntsbet and Saroftm lo be the major discrepancy of Ihe DDT/PCB ratio data. A recent review70 points out ihut dcgiadation products have not been identified for PCB's in aquatic systems, and flic relative importance of degradation and aed intent a lion remains to be assessed. Soedcrgrcn'1 examined the levels of chlorinated hydrocarbons collected in nylon nets at several sues in southern Sweden in 1970 and 197). The gcngtaphical distribution of PCB and DDT was distinctly diffeteni, with PCB's showing high levels (up to 10,510 ng pci m'* per month'1) in western Sweden and much lower levels (620 to 2190 ng pet m'7 per month'1) in caslcrn areas, whereas DDT shows little variation between sampling points. The higher residues in southwest Sweden presumably come from local Swedish industry with likely additions from Denmark and industrialized districts of West Getmany. Bidlemail and Olncy1' tackled the problem of the relative importance of particulate matter and free molecular form. They found that filterretained PCB were less th.m 1% from Bermuda of samples analysed in 197,3. A similar situation is found with the authors' values from Rhode Island17. although Bidlcman cautions that re evaporation from the filler may increase the free value. Bidlcman and Olncy found values of 2.1 to 9.4 ng/nt* for Rhode Island. 0.21 to 0.65 ng/m' for Bermuda, and 0.72 10 1.6 ng/m1 for the Sutgtsso Sea. Their value* are higher, by two orders of magnitude, than earlier work on otgano- IV of I'CBnt the v bin sc!tCVch ,1. Union 1 Not ili *. The tlf IUf pl.t til > tn .1 !: Aiiil.ii being -. Tli. DDT pICv)o'' DD1 ' with fete* .f wiici lues A. t\ St, s. i'll ^s tcsul* OCC.i lam Ctdn for a ptec,. ` stsl. , I- * Itcuduc levels sic sited in parts pet million {ppm! fulli.wtny usual tsiOvcrltitn. lists it cs|usvjlcnt lt< Mp/y 474 CRCCruittl Review! in Knvirownmttl Conirul t I i Itcfertnt't <ij Quinn cited in ct i. 1973 ** n at.. 1973 * mJ Qginn, 1974.** ,1 (.. 1974.*' dreed by Nisbet epincy of the h:il degradation il fot PCB's in importance of remains to be it of chlorinated nett at teveral i and 1971. The and DDT was ii'ing high levels t month"1) in levclj (620 to nt eastern areas, at ion between ics in southwest local Swedish in Denmark and many. (he ptoblem of tljie milter and nid that fittertun Bermuda of tilar situation is - from Rhode iilions that re* nutcase the free values of 1. I to t to 0.65 ng/m1 tig/m1 for the higher, by two work on organo- chlorincs in this area,1 1 but these workers collected samples using hanging nylon screens which only trapped PCB's attached to part utilales Eiichi and Ito1* found values around .1 ng/m1 in Nagoya, an industrial city in Japan. Current findings suggest that the atmospheric levels are higher and residence times shorter than suggested by previous work. These findings do not invalidate the general conclusion1'1 * that the aeiial route is much none important than run off in transpott of PCB's into the ocean. Recent studies have frequently failed to detect PCB's in rivers, i.e., Grove'* in the Rhine, and Sampson11 in major rivers and the Great Lakes of North America, 4. RESIDUE LEVELS The aim of this section is to tabulate the levels of PCB's at various trophic levels in different parti of the world- No attempt at completeness is made, but selection is made to cover a range of trophic levels and as wide a geographic area as possible. Unfortunately, studies outside Europe, Japan, and North America are eompariivety few The environmental levels in five major groups of organisms are examined- These are: (Il plankton, (2) fish, (3) oceanic biids, (4) aquatic mammals, and (5) lop avian predators. Additionally, levels in human food and in human beings are considered. The level* of PCB's tend lo parallel those of DDT and its major metabolite DDE. In the previous section on transport the movement (if DDT was considered at basis for comparison with PCB. A widely used expression of the relevant concentration it the ratio ZDDT/PCB where EDDT is (he sum of DDT and its metabo lites. A. PCB Levels in Planktons Stringent precautions are necessary in the collection of plankton in order to achieve accurate resulta. Grice ct at.** point out that as any ocean-going vessel is an abundant source of pollu tants such as petroleum hydrocarbons and pesti cides, the collection of uncontaminated samples for analysis is difficult. These workers give a list of precautions and consider that the internal con sistency of the data should be carefully examined. Jensen et a!.11 clearly showed that samples collected in the wake of the boat are strongly contaminated will) PCB's from Ihr bottom pauit Additionally, these workers showed that the chromatographic pattern of PCB's of wake samples resembled the pattern of PCB's extracted from the paint, whereas the samples from the how showed a difierent pattern. Harvey and Teal11 have shown that plankton can extract absorbed hydrocarbons from the nei, and further that the net is m equilibrium with hydurcarhott materials in the water, detritus, and plankton. A sweep of a net tlms samples the entire system rather than the individual components Ware and Addison1* sin died the effect of particle tire on PCB concen tration of plankton collected in the Cull or Si Lawrence. They found that there was a linear relationship between the surface to volume ratios of l he difierent si/e fractions and then PCB couictit. The levels nT PCB's in the 73 lo 102 uut particles ranged as high as 22 ppm on a wet werght basis and are easily the highest PCB concentrations reported in plankton. The values for composite samples (plotted on Figure I) are more in line with values for other areas. While carefully standardized procedures ire essential for monitoring of residue levels in plankton, there is no doubt that a global system of monitoring would udd lo our knowledge of the rale of transfer of pollutants lo the open (tecan The current knowledge of levels in plankton ate summarized in Figure I. The values fur the open North Atlantic are remarkably simitar In those from such polluted areas as the Baltic and she Firth of Clyde. The values for the South Atlantic ate considerably tower; unfortunately no values arc available fnr the Pacific. B. Residue Levels in Fish Europe - The data on levels in herring are summarized in Figure 2- The highest levels arc found in the Mediterranean and in the Baltic. The Baltic has been particularly well-studied and for additional information the reader is referred to Jensen eta).11*1* and West no and Noren.11 North America - Reinke el a!.1* examined the organochlorine levels in fish caught in 7# locations In Canada In 1970. Good coverage was obtained m Alberta, Saskatchewan, Manitoba, and Southern Ontario. Nine localities in the Northwest Territories were sampled, but none in British Columbia, Quebec, or the Maritime:. Values (or levels of PCB arc not given but authors stale "PCB's were quite prominent throughout the September 1973 475 HONS 206853 .1 I'tGUKL l. Global PCH't Icreti in planklon, Valuci art in ppm (lipid). i*;. Great Lakes and appeared (o a teaser degree in southern Lake Winnipeg in Manitoba and in (he Bow River in Alberti. In (he US , the first major survey of PCB levels in fish was made hy Henderson el at.1* Their data are mapped in Figure 3 and (he averages include those samples In wnich PCB's were not delected by plugging in (he value of the limit of detection, via., 010 ppm. They found that PCB's are a majm contaminant In fish, and, in two thirds of the samples, the PCB residues were higher thin those of tola) DDT, The majority of the high values arc found in the northeast, especially the Gieat Lakes, whereas Gulf coast and west coast values ate generally low so that the pattern is different from that of DDT. There is no suggestion of concentra tion around the site of production, viz., St. Louis. This survey was made in the fall of 1969, and no more recent national survey has yet been reported. Cair ei at 40 examined organochloiint residues in six species of fuh ftom many sampling points in Lake Ene in 1970 and 1971. Average values (or the 6 species ranged from 0.8 to 4.4 ppm PCB. considerably higher than those for total DDT which were 0.18 tn 0.90 ppm. These findings art in agreement with those of Henderson et at.1 * For Hie Atlantic const Zitko and Huixinger41 found that most marine fish had 0.2 to 0.5 ppm. Ziiko41 has examined levels in herring in the Marilimcs in 1972 and 1973 and compared them to the levels found by Addison ct al.41 in l*K>8 and 1969. Thcic ate some difficulties in that the data are not always strictly comparable, hut the majoi finding was that PCB levels have remained constant while DDT levels have decreased over this period. Caribbean - Ciam ei al.** sampled a number of different species of fish in the Caribbean from Florida, around the Gulf of Mexico to Yucatan The levels weie low, most below 0.1 ppm (wei weight), with the highest value 0 5 ppm near ihc Mississippi Della. Glim et al.4" examined teveli in the coral-reef dwelling Groupers and only 2 Osh on! of IK exceeded 0.1 ppm; the maximum value recorded was 0.2 ppm. 4T6 CRC Ciiuctl itrrirM In Enrironmrmtl Ccnlrot MONS 206954 0 '2 .056' / > SU22Z 0)21 r 4 4 ppm PCD. tot iota) DDT w findings tre <hi et ).** For /inger* 1 round * ppm Zitko4* tic Maritime! in hi to the leveU >68 and 1969. ihe data are not <c major finding I constant while period opted a number Carihhcan from no to Yucatan, v 0.) ppm (wet 4 ppm near the uinined levels in .md only 2 fish maximum value MCURI-; 2. Level! ol fCB1! In herring or aimllar ipecie! in burope. Top value! are total DDT. bottom value! PCB both art on wet weight balk. ' September 1975 477 o.e> OH :o.0/ 1.07 on .05$ ` L 0.74 ,'OJf' -043 7*-H < o.lITV\ J <04 |M> 0.77^ 10 7.17 - ta ?1* ------ 0.10 *7A->g.7'*(> '0 74 -O.S4 ALA3KA CHCNO * 7 43 KENAt n. t.tl -0.13 003 033 -o.to 1-0.7* AFTER MENPEftSON, (NOLI* 0 JOHNSON, l*7l ESTIMATED PCB CONTENT OF FISH IN PPM. DETECTION LIMIT 0.10 PPM. KIGURL J. Level* of FTH'i in fish in the U.S. Values it( In ppm. on wet wcijitn ham. Japan - High levels hive been found in both fresh <tnd salt water fish in Japan/*'47 Based ttn S95) samples, Fujiwara47 reported that 16% of the samples exceeded I ppm and 3% exceeded 3 ppm The taller value is standard regulatory value in Japan. Doguchi44 summarizing results on 2.R26 samples round (hat 141 or 5% exceeded ihe 3 ppm limit. They concluded "that the pollution by PC&'s is dangerously advanced in the aquatic environment around the megalopolcs such as Tokyo and Osaka and other industrial dislriels, and some species of fish in these areas are unfit for human consumptions." Southern hemisphere - Solly and Jiirrison41 did not detect any PCB s in any species of fish, crustaceans, and mollusks from buth fresh and coastal waters of New Zealand. Ncuhaus et a!4* examining for residue levels of urganuclthirincs In several species of fish in Australia, did not comment on the pretence or absence of PCB's. C, PCS Residue Levels In Sea Birds The residue levels In sea birds, a diverse group of birds, have been the subject of many papers (Table 8). The information on two species for which there is dear evidence of reproductive failure in some areas where organochlorme residues tire high avc given in some detail. These species are Ihe hening gull and brown pelican. The possible causes of reproductive failure are con sidered later in this review (Section 51 Additionally, data on pclapic sea birds, mainly shearwaters and storm-petrels (Pr<cellariilV>rmes). are summarized as for this group the widen geographical information on residue levels is available. One difficulty in building up a global picture of Ihe residue levels is the highly migratory nature of some species. The sooty shearwater, fin example, breeds on remote Islands in the southern Pacific and then migrates around the basin or the Pacific passing dose to such industrial areas as California and Japan. Ollier species, such as the snow petrel, remain all the year in Antarctic waters. In some cases, notable sea hiid kills have been examined to assess the likelihood that orgunoclilorines have been involved. Herring gulls Hits species is dusdy associated with man, paiiicdlarly In wittier when scavenging in garbage dumps is a way of lilc Noi surprisingtv high residue levels have been found th some areas, especially those from the (Jrcai Lakes of Nurih America. Reproductive success in some colonies in Lake Ontario have been very low.*0 (These findings are considered in more detail in Sec dun 473 CKC Critical H (viewf in t.nvirnnmemal Com rut NONS 206056 S) The N v)A ic detail. These -wn pelican. The failure are con- (Section 5). i birds, mainly tcellariiformes). mp Ihe widest \tdue levels is ting up global highly migratory shearwater, (or - m the southern ihe basin of the dust rial areas as res. such as the ,rr in Aniarclic a bird kills have likelihood that <1. loscly associated when scavenging Not surprisingly, nd m some areas. Lakes of North some colonics in low.** (These Jrtiil rn Section S). The residue level* in eggs of thr* species arc summanMd in Tabic 6. Bjerk and Jloii*1 examined (he levels of ITU's in 10 colonics in Norway. The variation was small, ihe mem values ranging from I.SB ppm in southern Norway to 0.63 ppm halfway up the Atlantic coast- Tire value for a colony in the extreme north was 0,74 ppm. In all cases the liDDT/PCB were between 0.44 and 0.H7, The residue levels are higher on the Atlantic coasi of North America, bui Ihe levels of ihe colonies on (he Great Lakes showing marked reduction in breeding success have levels an order of magnitude higher. Brown pelican - The dramatic failure of the reproduction of this species off the coast of California, first noted in the lale 1960s, was one of the cleat-cut cases of a man-made chemical having an effect in the environment. In this caso, the levels of DDL are much higher than l*CB`s (ratio nf area 0.2) compared with ratios of 2 to 3 In Florida, (Table 7). In the failing colony al Anacapa the levels of PCB's arc well below those of the herring gulls m the Great Lakes. The DDL levels are considerably higher and the main cause of failure, egg shell thinning followed by breakage. is oulstdc the scope rtf this review. Siinrhrly Blus et al.1* considered Dial DDF, was the main agent in the failutc of brown pelican nesting in Smith Carolina. Sea bird kills Several large kills of sea buds, especially alcids. lit ihe Irish Sea have heen associalcd with high residues of PCB's in the bodies.**'** Purstnw and Jefferies** found that the mean total body burden of ITU's in guillemots was 4,660 fig (btrdy weight S60 g) in birds found dead, about twice (hat found in apparently healthy birds collected in lltc same area. Due to loss of much of their body weight (the healthy birds weighed about I kg), the levels in organs were much higher in the birds found dead than m those collected. Ilicsc authois conclude that PCB residues may have contributed to but not been thr initial cause of moitalily. Lloyd el al.** examining a later kill, also concluded that no definite cause of mortality could be established. Littcer and Pcakall** reduced the food intake of ring doves preloadcd with Aroclor 12S4 such that the biids were losing 10% body weight per week. No differential mortality was noled with controls and the liver Icvch of ITB's were some 20 times higher TABLE 6 Residue Levels in the Eggs uf Herring (lutls Location Norway Naw Hrufuwtrk bay of I'undy Quebec Lake Ontario Lake Hite Lake Huron Lake Superior Southern California* Vear of collection 1969 1969 - 72 1971 1972 197} 1969-72 1973 1972 1972 1972 197) 197} n 0* 5 13 15 15 16 15 16 6 5 6" 12 DDtitppm) Killppm) Keltic nec 1.53 (W) 14.1 tl 2.5! (W> 1 32 tW) 2.10 (Wt 32.1 (lit 134 (1)1 lit (l)> 4*.o an no tm 15 9-33 9 (W) 11.1 (W| 1 00 (W) 25.4 (I)) S3 3.3 3.7 65.2 (Wt (Wt (Wt <1)1 420 (1)1 565 300 tin 36* tin 40.6-64.1 (W> S.t tW) Bjerk and ttnll* Cilhcilson and Rcynotdi' ' Zilko*1 Gilbertson and Reynolds" Teeptc" Gilbertson and Reynolds' * Rydei" Hunter al." Summary frnm 10 colonies. (I ni detail* see tcxl l *Si> pooled sample* from three colonic*. *Gosely related western gull, n - Sample size. I W _ Wet weight basis. [ D - Dry weight bails September 1975 <79 Location Florida (Gulf coait) Florida t Atlantic eoaill South Caiolina California (Anacapi) South Caiolina Florida Florida (five colonici) California (Anacapi) (LotCoronadoa) (San Martin) (San Benito*) (Gulf of California) SocctmM neiti. "Uancnnriil Milt. W - Wei weight. L - Lipid wciphl. Ratio W.Lcitce 1:10. TAIILI 7 Reaidue Levels In Blown Pelican L|p Yeer 1969 1969 19*9 1969 1971/71 19*9 1970 1969 and 19 7o 19*9 and 1970 Sample me 17 12 II to ll* If 14 11 17 *5 28 * 10 4 DDLtppin) 1.17 (W) 2.24 (W) 5.24 <W> 71 7 (W1 l.7(W) 3.23 (W) 17 (L) 16 IL) 26 ID 117* (D 1109 <L> 419 (L) 111 (L) U (L) PCHtppm) 0 *9 (W\ 2 II IW) HI (Wj 16 <W> 5.50 (Wi 7,94 (W) 120 (L) *9 IL) 71 (L) 110 (L) 1*6 <Lt 71 (L) 19 IL> 4 IL) Reference Blue ti el." Bhiictal" RMimiV R taebrooyh'' TABLL I Realdur Leveli of Scabirda end Their t-jfi Local k>n Special Tiaauc Aacention I aland Central Atlantic Maurliiui Central Indian Hallelt (aland Antarctica Palmer Station Antarctica Rota (aland Anlardiea South Oikneyt Antarctica Palmei Station Anlaictica Gracnland Sooty tern Fairy (ern Trinidad pet ml WdeofTi petrel Snow petrel WHaon'a petrel Adelle penpuin Chinatrtp penpin Skua Skua Brunnkh't |ulUcmot Liver lit Liver and rat tw> Whole body WMe body Wliiic body Fn tat lal Liver Ebb* I'ei W - wi wei|ht. D - Dly weighl. L - Lipid weipht. n.d. - Not delected. n.e,f. - Nol ea mined for. l)l)L(ppm) nd n.d. n.d. 1-4-2-S (U) 11 (L) O il (t.) 45.8 (L) 0 O.tttW) 0.0 U-0.041 (W) 5.8 and It 0 (W) 4.0 and 0.9 (W) 8.7 (L) 1.5 (1)1 l.l-S.l toi pCH(ppm) 0-9.1 (L) Trace n.d. 11.0 (L) 0.14 (L) 185.1(1.) n.e.f. n.e.f n.e.f. 45.1 <L) '2.9 ())) 1.9-19,6(0) Rrfcicnce Johnilon" Johnalon'* Johnalon" Temple end PcakalT*' Riaehrnugh end Carmipnanl* ' Ceoiyt and Fleet*1 Talion and Kuticka* KiMbnmph and Ceriuipnani*1 Buealrup ei at * * 4B0 CRC Critic*! R eriewt in Cmironmrnttl Control MOMS 206858 LiviUm Davie Su n' T v tititl jtt CUr*rm.t Nw / v S<mth liti t New 7r.i(.K C.nlk Sall.'i: Nvw /t\tl ii Su.lU'S Iv1 > Nc v. /cjl.i1 Aih U.nul Nvw /i ll llv.m di" evidence moi i.ill: D. Let i A it in in;n i' iiid nn levels o' `)| Lr.t from a 1 |1|H1I i: Jvow i tnjil n. vtlll.ll I I lolisi I Adili'Can.n1. in l l it. Utio'- . ftHIM J JIIUi.1 mu fn jtii b. lit ` funnri Sl'.iIi Reference glut ei tl.1 * Blui ei il." Ritcbrough'' Ruebrough' * Reference union'* union" 'inston" uple and Feikalt* * wbiough end armtgnani*' ni(t tnd Freer*' `Hon tnd Ruticke*1 -chough tnd wmignani'1 acstrupei el." TABLE 8 (conriniicd) Residue Levets of Stablnli and Their L$p Local ion Specter Davis Snail laiocs 40*N 4*W Trinidad Cslifoinia Puffin Common guillemot Fuinitr Gtcal shcirwitci Fulmar Sooty shearwater New Zealand Snulb Island New Zeatsnd Cook Shail While-fronted tern I'stry prion Diving pelrci New Zealand Snirei island New Zealand Auckland Island New Zealand Diving petrel Sooty iliearwater Sooty shearwater Sooty shearwater 1 istuc la! Liver Liver Liver Livei 1 ai Livei Whole body Whole body l Whole body Bteasi muscle Wholebody lit. atiuh lal. chick DDItniitn) - - _ 4.4-5.3 (L) 5 5-3 9 (L) 1.4-7 9 (L) 0.03 - 0.75 (L) 0.5-1.7 iL) 7.3 tL) 10 6 19.7 (L) 1.30.1.77 (LI P< "tit ppm* Mrfctcnir 0.5. 1 7 (W't ti.ti.t. tv: h i-04 Oh- t.l 17-59 32-103 0 5.07 0.4.3 4.I7.S (W) Huurne and Hugs Riarbiuufh ct ai 7.3,10.3,17.3 fW) 14 -1.4 iL> Bennington ei at 0.4-3 3 (Lt 7.1- 3.3 (L> 0.5-0.14 (LI 0.X-1,7 (L) 7.4 IL) 1 i 7.7 (L) 0.05,11.1 i (LI Diene* ' than those found in tea bird kills. Thus no alrong evidence exists to link PCS levels with set bird mortality. D. Levels in Marine Mammals A &ood deal of Infunnalitm is available on levels in marine mammals. These species are long-lived and most arc a< (he lop of marine food chains. The levels of PCB follow expeclcd patterns (sec Table 9). Levels in the ringed seal, for example, range from a hundredth of a ppm In the high arctic lo 20 ppm in (he Baltic. The values fix the grey teal show high values near industrial sources in England. The 1DDT/PCB ratio shows considerable variation. Values about unity were found by Hdden71 for both sides of the Atlantic by Addison el tl.11 and brink e( il T* In eastern Canada, and Bowes and Jonkel74 in the Canadian arctic. However, Clausen el |.7* found very low ratios in weatern Greenland and Jensen ei al.,s found very high ratios in Ihe Baltic. The small amount of data from the southern hemisphere confirms Ihe low levels of BCR's foond in pelagic sea birds and fish (Figure 2. Table 8). Both Frank el al 71 and Addison e( il.7* have (ound a distinct increase of PCB levels with age in seals. E. Residue Levels in Birds of Prey The birds of piry have been extensively studied in connection with contamination with organocldorinc compounds. Studies are particularly detailed on the peregrine falcon, This species breeds on all <he coitllncnis except Antarctica and. being highly prized by falconers, there is a good deal of background informality on this species. A technique for eluating the membranes of eggshells from museum collections*4 has enabled studies to be made on residue levcti front the time of rust usage of the persistent organochlorincs. This daia, together with that obtained by analysis of Hie egg Contents, is summarized in Table 10. Although levels in the southern hemisphere are a good deaf lower than in the northern hemisphere, appreciable levels arc present in the eggs of this (pp bird-eating predatoi throughout its tangu. The hald eagle of North America and the witit Mailed eagle of Europe are similar species which feed largely ini full. In Faoo|>c, Kormanet al.*4 report residue level in eagle eggs as ft to `17 pptn (wet weight) m 22 eggs collected from 1969 lo 1971 in Germany The range of values of DDE was 1.2 to 17 ppm. A single dead eagle had 35 pptn PCB and 4 pptn DDE In Its liver. Even higher values, vie., 157 ppm HCB's September 1975 411 *, , \ I I I l L I ! MOMS 206859 TABLl'9 Levels H> Seals and Oilier Marine Mammals Rctidwr*. Spec in Rinpcd iel Locality Arctic Canada Altlic Norway Bailie C.uir of Bnlhnic Wes l cm Greenland James Bay Western Greenland Antic Ocean PCS 3 ls 21 13 09 10 0 16 001 19 tUDT 2.1 24 23.8 130 0 15 1.3 U. 18 016-2 8 Number 3 3 i * s l 1 17 Harp seal Gulf of Si Liwrcncr Newfoundla nd/Labrador Jan Mayen Barcnt Sea Gulf of Si. Lawrence Newfoundland/Labrador Gulf or Si. Lawrence Hooded seal Gulf of Sl. Lawrence Western Greenland Grey teal Bailie Gulf of (inland Stockholm Archipelago Orkney, Scotland Western Scotland 1 jtlern Scotland I jslcrn l.nyland Wales Gulf nf St. Lawrence Western Scotland l ames Island Eastern Eri^and 12 1.2 IS i.y 2 6-10 1.2-26 2-22 3 2.7 30 6.J 13 IS 16 30 38 123 212 27 32 14.4 31.0 1S2 6 3* ll SI* oso* 094* 4.5 1116 10- 50 0 3.1-22.6 10.2 029 130 42 130 13 91 13 20.1 39.7 17. S 4S 49 7,4 10.7 IS.S 56 6 7 S 24 54 IB 1 S 8 7 16 2 3 7 6 7 4 Bearded seal Western Greenland Halbor seal Ma me New Brunswick 1.8 92.S 41.0 0.47 6S.4 31 0 S 6 4 PC iiDOT** California Orcpon Washington Alaska 6H) 62 162 11 - * PCD lddt Holland (juvcnllcl Holland (adult) California '40 ',470 Nol Haled 2 9.5 IB and 158 3 S 2 Bot Unnoted ItoUand dolphin 35 20 5 2 Common dolphin New Zealand Noldeleeied S3 4 4B2 CRC Crihetl Foric** in knvironmmtal Control Reftumcv thildcn'1 Jcnn-n el at *1 Clausen el al " Bowes and Junket*' Pearce el l** Holden citedm Pearce ei al Hank el el. ' ' Addison cl al '1 Hidden" Clausen cl al," Jensen el al.' * Holden'1 llcpidcslon* ' Clausen el al." Gaskin er at'* Anas'' Kitcnvm et il.1* Shaw" kncmqACl ll M Kocminetif** S|H\ K Su'tHJI.i Il.tlto" I'Olpmt St -t |ltll t mb.td ihun wi.. *nm **Oi:K 1 limn/ * I I 1 TAHLL 9 (comimicO) Levelt in Seali and Other Marine Mammal! Rcfiilnci ppin (blubber) Specie* Sur iru m dolphin Hatbnr porpoiec Scallop Locality Dutch Guiana Nonh Sea Weil cm Greenland California Pen Not detecied 1.DDT 2.7 U 6.7 112 17 41 03 R24 103 Numbei 1 Reference Liftman cl al.** 7 Kiicman cl at.** 2 ClaiKcn cl al '' 6 IK Long rial*' 4 finback whale North Atlantic Pitot whale Caiibbcan 001-0.11 0.69-5.00 0.66-2.56 1.25-7,31 Saubcnbtecher* * Gaik in cl al.** 'DOt only. Only one utnplc analyzed for individual compound'; thi n 1.100 ppm DOC, 96 ppm DDT, and $72 ppm PCB "tcivinf biith to premature pupt; other lamplc going folt-teirn. TAB1.L 10 OrginocMurine Leveti in frrtgrine l|p Lucalily Date and tample aiic DDL Ippm, w) PCB (ppm. ) Technique Reference Amthltka, 1971-73,10 Altnliani Interim 1971-73; 10 Alaaka Greenland 1972; 1 California 1941-49:3 Colorado 1950; 2 1973; 4 Gteal Britain 1962- 66:12 1967-71:54 Chile 1966; 1 ScHiihwetitrn 1970; 1 Africa Aniiialta 1949; 1 1*51; 1 New Zealand 1973; l Auckland Dland* 2.5-7 41-10 36 3-9 4, 30 33 4 4-21 4 2.3-10.1 1.5 10 17 3.1 3.1 5 SO Whole egg 32-60 Whole egg 40 n.d. n.d,, 15 S.t not determined 1.0-4.0 4.0 1.0 Whole egg Membrane Membrane Whole egg Whole egg Whole egg Membrane Membrane n.d. Membrane nd. Membrane 4.9 Whole egg I'cjkuH cl el.** Walker et al.** Peakatl* *'* * Ifodc raon and Craig' Rahllffe** prakall and Riff* * Peakall and Riff*' Bennington el al.** Qnidy related Nee- Zealand Vatcon. W * Wet weight n.d. - Mol dr acted. September 197$ 413 HONS 206*61 and 172 ppm DDE. were recorded Tor two while-tailed eagle eggs from Uie Gulf of Bothnia*1 These level* are high compared to those of the bald eagle from the U.S Alaskan Eaglet in the Kodiak area averaged 2,2 ppm (range 1.4 to 5.4 ppm), and those from the Admiralty island only l .l ppm (0.4 to 2.3). From the continental U.S. values ranged from 2.2 (Minnesota) to 27.7 in Michigan. Five eggt out of 11 exceeded 10 ppm Residues of DDE were distinctly higher** Brain levels in adult bald eagles Tanged fntnt nace to 65 ppm in 1969 (n 28) and trace (*: 230 ppm in 1970.** Levels of DDE were similar, but median values were lower. F. Levels of PCB's in Humans and Their Food In considering the problem of contamination of human food by PCB's, It Is necessary to separate occasional accidents leading to serious but local problems from the "normal" background level. In Japan, PCB's leaking from a pipe in a food processing plant led lo rice bran oil containing up to 1,500 ppm of organic chlorine comprninds. The main findings of this occurrence, termed "Yuiho," were described in a special issue of Fukuoka Ada Mtdieo in 1969.**'** In the same year contamina tion of some two million chickens occurred in Japan1 *- at a level high enough to cause symptoms similar to chick edema disease. Over a million chickens were destroyed in the U S. in 1972 after accidental contamination.1* ' While lhee accidents produce the moil serious cases of PCB poisoning on record, they are the result of carelessness and the main concern of this review is to evaluate (he effects of overall environmental contamination. The question of (he role of chlorinated dibenzofurani, which occur as impurities in PCB's causing effects ascribed to PCB's, is a difficult one to evaluate. The chlorinated dibenzofurani are much more toxic than PCB's. Severe and lethal liver damage in rabbita hat been caused by 0.5 I o 1.0 mg/kg.,#l***'* Thus, the chlorinated dibenzofurani are some orders of msgnilude more loxic than the r'.iorfnaled biphenyl*. The chlnrinsted dioxins are even more loxic with LD0 values as low as 0.6 ug/kg reported for guinea pigs.,0lC Vo* et *I.,,T found 5 ppm of penta- chlorodibenzofurani in Clopen A60 and 20 ppm in Phenocior P60, bul less than I ppm in Aroclor 1260. These differences In Turin levels were correlated with differences in toxicity. 4M CRCC'iUctt Rtutwt in tnnronmtntil Control Attempts to detect dihcn/nfiiratis and dioxins in wildhre samples have filled,'011''0,1 bul these studies were carried out in Canada and (lie U. S. Studies in Europe, where the levels of chlorinated dibeu/.ofurans ire higlscr. would be of interest. Recent studies in which PCB levels up to 100 ppm weie fed in ducks icsuliing in tissue levels up to 3,000 ppm, failed to reveal chlorinated dlben/ofutons. Ih In litis study the initial levels of furaos was about I ppm. The possibility that highly loxic impurities are involved in actions ascribed to PCB's is real, bul lias rarely been definitely demonstrated, A sampling of levels of PCB's in food are given in Table II. As might he expected, lewis ire highest in fish (see also Section 3.3), In oilier foods the levels detected are low. The tentative acceptable daily intake in the U. S. lias been tel at 150 lo 300 pg/day,nl. whcteis the avetage intake has been calculated lo he only 7 pg/day.1*1 However, * study by Price el al,1*4 on the diclof 8 girls in Virginia found that while 4 had only traces of PCB (i.e.. less than 0.001 ppm), 4 contained 200, 420, 580. and 840 pg/day. In certain areas, viz., northeast U. S., Japan, and much of Europe, persons citing considerable amounts of fish would be expected lo exceed the FDA guidelines. Levels nf PCB's have been measured in human adipose tissue and in human milk (Tables 12 and 13). Wlieic possible, the residue levels of PCB's are compared to (hose of total DDT. In general, the levels of PCB's arc lower than total DDT and in tome cases PCB's were not delected, viz., adipose (issue and milk from Texas.'**',Q* In (he tout hern hemisphere PCB's were not delected in human* from either New Guinea1** or Australia'*7 despite the fact that DDT and Its metabolites were delected in both groups. Finklea el al.10* examined the level of PCB's and total DDT in 723 plasma samples from persons in Soulh Carolina in 1968 (see Table 14). They found marked differences in the levels of both compounds by holli race and residence. The PCB levels ran from a tow of 0.3 ppb for rural blacks (with less than 5% positive) to 3 1 ppb in rural whites (with over half positive). No signifi cant variation was found by either age or tex. Considerably higher levels have been reported from Japan, where healthy persons were found to average 10.6 ppb and PCB-intoxiciicd patients averaged 18.3 ppb.1 * A similar elevation in persons suffering from i 11,i *t" ltd..., Ci* I'. live I . Chi Out' Hull *Onf ft J "Kanemi YuC alilimiph thi workers fuini.i 2.7 ppb, uih.iipatients of 7 0 patients over i, small, but tl. years alter ih. examined tin and blood pi values (n = Pi 4.9 ppb in pi. levels for mil.', equiltbrium IDDT/IVH r 4.9 fot plasm i Hesselherp of PCI! ami Oh carciiu'tuas an,. They found r nonpalicnts ;i persons. The patients ei incieasc in p l dioxins in bui these l the U. S. Iiiorinated f interest. 11>0 ppm vcls up to 'I dibenzoI levels of itiliiy that m actions irely been ,! ne given levels are i. In other c tentative hcen set at uge intake pg/day.10* the did of 4 had only 1 ppm), 4 ug/day. In Japan, and >msiderablc exceed the I in human hies 12 ini f PCS's lie general, tlx 1>0T and it i/.., adipoai ** In tin detected in ura`*` or >[)T and ill in. cl of PCD a tuples fionr c Table 14). lie tevcli of sidence. Tt e |>b for mril o 3.1 ppb i. No sign age ot it rn report- :d etc found lo icd patiei ts Ifcring from Tabi.i: tt Levitt In Human Foot! Riod Area PTll level Reterens'e Ti,h (various species) U.&. (Atlantic and Cult coast) Valuer ranpiny up lo 0.65 pptU, 66% positive Markin cl at.' " Herrins oils i-jslern Canids 1.7 |o i 0 9 ppm Add-on el at.*1 Cribs Values up >n 0.15 ppm, 66% pfisii ive Seer fit U.S. Occasionally present < 1 O'/Spositive), maximum value 0.69 l ord el at.11 Cheese Canadian Isurupean 0.01 lo 0.17 ppm* 0 01 In 0.01 ppin Vitlcncuvc rt at.' Chicken cm Canada Japan Butter * Norway Japan Mean value 0 000 ppm, 100% polilivc n.d. - 0.01 ppm 0 01 to O.Ot ppm n.d. - 0 01 ppin Mrset at."' Fujiwara* ' Bjcrk1' * l-'ujlwira*' Marine products Japan 0.005 lo 5 ppm t'ujtwara* ' Only une value above 0.6 ppm. ltd. - Nut delected. i "Kanemi Yutho" wai found by tnoue et al.," although the actual valuei were lowei. These workers found a mean value for rural persona of 2.7 ppb, urban persona of 4.5 ppb and "Yoslti" patients of 7.0 ppb. The elevation of PCS levela in patient! over the normal population is relatively amall, but these measurements wete made five years after the Initial poisoning. This group also axamined tltc correlation of adipose tissue levels and blood plasma levels.111 They found mean values (n 17) of 1.6 ppm in adipose tissue and 4.9 ppb in plasma. No correlation was found in levels for individuals, and It was concluded that equilibrium had not been reached. The XDDT/PCB ratio for adipose tissue was 3.8 and 4.9 for plasma. to be due to loss of body fat and hence to increasing circulating levels of organochlorines. The change in the ratio of DDT to PC8 front nonpalicnti to patients is surprising, and the final level of PCS'! in the blood is high in the latter group. No PCB'i could be delected in human embryos from Japan and levels hi fetuses were only in the parts per billion range (2 to 28 ppb) at term.11 * Again in I hit study the levela of total DDT were higher than those of PCB'i. The EDDT/PCB ratios in liumaus are typically above unity and thus different from most other top predators. 5. PHYSIOLOGICAL EFFECTS OF PCB s Hcsselberg and Scherr1'* examined the levels of PCB and DDE in palicnls suffering from various carcinomas and from apparently healthy adults. They found an average level of 3 ppb DDE In nonpitients and failed to detect PCB's in these persons. The corresponding values in cachetic patients were 21 ppb DDE and 47 ppb PCB. The increase In patients suffering front cancer is likely The physiological effects of PCB'i arc consider ed mainly on a class by class basts, in general, lire effects ate sufficiently different from mammals lo birds to Dili to make this the most convenient way of handling tire data, In some cases, notably en/.yme induction, the data lend themselves to a wider consideration. Acute toxicity is considered Itrst, followed by effects on reproduction. September 1975 485 UnU of K'l i and DDT in 11 u man Ailipixt Tjiw I*C"nippm) Atci US. (Michigan) Dale 1971 Meant lange) Negative Tract in 10 1 0 tu 2.0 Z.O 7M number) 2 Of* 4) 55 6*1109) 36.7*<72> s.67mi) Mcanltanpi!) Not staled Rcfcirnce rrite and VVelt U.S (Michigan, 1968 69 riorida. and Culoiado) Negative Tiace in 1.0 1 11 tu 2.0 Z I) >4 27M2JS1 Nnl ilalrd 27 XMIIRS) S.27HJ6) Yobs' ' * U S (Texn) 1969 1970 197) 197 Z Nut dcicvlw! Nui ilcleclcd 1 Tt0.6 in 9.9) Natl detected 13.0 21.0 22.) 29.3 urns'** Norway (Oslo) (Rikihoipitahrt) 1969 70 axtuo o in Z.T.1) 0.60(0 23 m I t)) i 90(0 It t 6,72) 3.18(0.61 In 9.40) jerk'" Germany Austria (Vienna) 1974" 197 J" 6.8 tu 10.0* 3.S 3.8 tn 7.S* 4.6 Ackpt and Schulte1'' fscnduKet *t it'" Japan (Tokyo) (Kyoto) 1971-72 1971 2 H0.7 ip J.t) 4 7(1.9 lo 1)3) Not dated 9 8(4.2 to 14.8) tJoguchi* * l:u|iwaia* ' 1st ad 1974" 2 75 9.94 Wastcrmann' ' 'Meant from five eitte*. "Vtat of publication. Notes.' An catty repurl or ZOO and 600 ppm' "in twu sample* it pieeuutahly in error. Addiliunal references of data I mm Japan are (Wen in DoguchL' *1 Valuer are niutHai to thole cited above. A. Acute Toxicity Mammala - The acute toxicity of PCB's ii low compared to mutt organochUwlne pesticide*. Grant and PltOltps1 ** found U)l# for rai* of 1.3 to 1.5 g/kg for Aroclor 1254 with younger rati having somewhat higher value* titan older animal* and virtually no difference between the icxct. An LD1# of 4.2 g/kg for Aroclor 1242 wa* found by Druckncr el al.1** Value* around 29 g/kg have been reported for mice,"4'' '* and Ckgg"* cite* value* of 8 tu It g/kg for rahbtii. By eontparitnn. the LD*n for rat* of DDT ii 0. II g/kg. and dicldrin 0.06 g/kg.1*1 tn feeding experiment*. Tucker and Crabtree* ** found 100% mortality in rail fed 1,000 ppm Aroclor 1254 within S3 day*. Kimbrough ct at.'** fouttd only 50%mortality at lire same dosage in an K-tnontli tludy. An tnomalout situation is Hie high sensitivity of mink, in I hi* specie* 3.6 ppm Aroclor 1254 produced 100% mortality within 105 day*.14* The repro duction of this species is also very sensitive to PCB'i (see next sect inn). Birds - Heath'4* measured the dietary Lf,* for several different Aroclors. Their definition or U\,, was the ppm of a chemical in an ad lihtlum diet expected to prodocc 50% mortality among 2-week.old birds in K days, with 5 day* of inxic diet followed hy 3 days of untreated diet. These workers studied four species of birds, viz., mallaid, plicasant, bobwhitc, and Japanese quail, and six Aroclors (1232 to 1264). In general, (he toxicity 416 CUC Critical H mem In tfnironnicntal Control MOMS 206S64 US ((. t'ft't t I C\J` t i N. NsfKl.1V |() lb Shttlcn ttpslis^nv liil'.in fkb Nv\* (Juir,- Aiuiral* i *1> in ,-t r. `Hiving l/vrl* n( \ llufTIlfll HcMtk'nv t Hiit.si. : t'rls.in. i* Hthjn iliijl, ^ Al(vr 1 ' T., nm is K. MV ' nf tlic ' ctiiori't. except > values w;t< Ui mp/kc Hun cm oveili!| < Sob' quail Reference ,t and Welch' * * ISTPl' ** iftk *11 I, kc< and Sihuhc"' l\rnd(irfci cl ?)'* I inpuclil4 * I ujiwita* 1 tt;iMCimnn' ' * rrenets of del? fiutn <0% mortality at nilt study. An nsiiivity of mink: i 1254 pioduccd The repro* very sensitive to ihe dietary Lf ** > licit definition of .il in an ad libitum mortality among :lt S day* of loxic iicited diet. Tltetc 1'iidi. vil., matlaid. **e quail, and fix ncral, the toxicity Lrvcit nf FCB'i nd DDT in llunun Milk Are? U.S (Cnloudo) (Texas) Canada tNew tliun'w,r kt (Kiiva St un?) Norway (Oslo) (lleilffn) Dale 1971 72 1971* 1972 1972 1969 71 y PClKppiu) meant w <1i 04 in 0 lOt Nisi detailed ttdl 2rtni' o. oojtn UOIIlOOII in 0 U 321 not noomoim OOUdiece tn 0 02> DI>Tt ppm) nteanfranpc) (0019 lo0 3K(.) Present (I.03MI1017 tn O.tKiR) U.0I V<0.(K>9 in 0 0.'ll 01)54(0.01 tn n;: 0 (177t(f*t (U 0.211 Rrltmitf Savage ct at " Djinenr ct at.' ** Mnsiatei A ` Bicii'4' Sweden 1971 72*' 0 025 (1059 WesliKund Novni1 '1 Get many Jepen (Kyoto) 1970* 1971 0 103 005(001 |.i 0.31) 0.081 0 095l.00b lit 0 44) Ariel and Schulte'11 llijiwei?*' New Guinea 1971* Nut detect ed Pinenl Hymen 1 et at.*" Austtaiia 197 J* Not detected 0.064 Siyali' *' Date of public?(inn. Weitoo1 '* stater llut the average HCB level in human milk in Sturkhuhn coins lu have increased flow 1967 to 197 2. TABLL 14 Lcvch of PCIt anil Total DDT in Blood Collected ftom Humans in Souih Catotina in 1968 Mean plasma residues tppb) Residence, race rcR Total DDT Sample sirr Rural. Mark Urban, Mark Uthan, white Rural, while 0.35 1 97 24 3.2 209 12 5 4.7 5.6 139 173 199 210 After l inklca. J . Plicster, t. I. , Creatim. J. f., Ileum, T., limners, T , and Itammci, 1). I., Am J. PuMk 61.64 S, 1971 of the AroclofS increased aa ihc percentage of chlorine increased Although there were some cxcepllims. Some tpeciet variation was noted: tlic Japanese quail was rise least sensitive with LT* values ttf 2,IH5 tn 5,000 mg/kg and tlic bobwhne was (he moat sensitive with values of 745 to 3,000 mg/kg. In general the toxicity or Aroctors was less than either DDT or DDE, although ihctc was some overlap in tlie case of DDE. Subsequently these workers' *5 fed Japanese quail diets containing Arne lor 1248, 1254, and 1260, such ilia I Htc birds received equal amounts nf chiuiinc in iltcir feed. It was concluded that while toxicity was positively correlated with rite degree of chlntinaitoit, it is nut simply a function nf chlorination. Harris and Rose14* found a reverse situalinn m chicken - a species not studied by Heath and ctvworkcts - in that Aructor 1242 was more toxic lltiitt 1254 which in turn was more toxic than 1260. Fish Wildish144 found that rite leilul llircsholit for (ininnunit iHtvitmiy was 0.001 lo 0.01 mg/l fot colloidal sotulioos of Aiocior 1254 and 0.01 (o 0.1 nig/t fot Ari'clnr 1254 solubilized in an emulsion. Hatlula and Karlog'4' found a linen relationship between rite time fm 5077- mortality and the log of the concentration of Gophen A50 for goldftsii. With a concentration nf 4 mg/l, Ihe lime for 50% mortality was 5 days: at 0.5 mg/I the lime was 21 days. Hansen cl at.'44 found that Ihc time fur 50% mortality for pinfixli exposed to 0.005 ing/l Aiocior 1254 was 12 days and 18 days fur spot fish. Tlic tatter species was not affccled by 0.001 mg/l. Morgan'41 found riot 2 mg/l Aroclor 1242 caused 100% mortality of guppies, but only 25% mortality was caused by 0.2 mg/l. Septeillbti 1975 48 7 HONS Z0*S*5 Crutiarean* - Duke e( a).'** found that 0.1 mg/l caused 100% mortality of juvenile pink shrimp within 48 hr, whereas 0 01 mg/l (lid not cause mortality within this period. Complete inhibition of oysier shell gmwlh was found at 0.1 mg/l; at 001 mg/l, the inhibition was 41% and at 0.001 mg/l. the value was 19%. Insects Lichtenstein ct al14* found that PCB's were 40 to 300 times less toxic than DDT to huuse flies and fruit flics, the toxicity decreasing is the chlorine content increased. Mnrnniy,,# found that the grasshopper lud a low suscep tibilily lo Arnclor ) 254. II is clear that the acute toxicity of pure I'CB's is low compared to either niguimchlnrine com pounds in widespread use. such as the insecticides DDT, dieldrin, bcn/jcnchcxjcltlorfdc, aldrtn. and endrtn. B. Liver Morphological Changes Morphological changes in the liver have attracted a good deal of atlcntlon, suiting with a study by Bennett cl til.1*1 Inhalalion studies (0.S7 and 0.93 mg/in* 16 hr/day for up to 143 days) on rats ted to livers which were pale, nr slightly yellow and mottled. The mosl conspicuous change was hyaline degeneration, Increased pinmitrerwe of cytoplasmic granules and increased vacuolization. No increase in liver weight was noted. Most rats given 3 g daily (05% chlorine) died, survivors showed enlarged livers with swollen cells. Al a dose level of 0.5 g on altermiie days enlarged livers (33% increase) were seen, with large numbers of acidophilic hyaline globules in the cytoplasm. Nishintmi'*1 examined the fine structure of livers of mice and monkeys exposed to PCB's. The dose given to the mice was high, 0.5%, but the dote given to monkeys was 1.4 to 16 mg/day. The most marked alteration was an increase of the smooth endoplasmic reticulum and a reduction of the rough endoplasmic reticulum. It was con sidered that this proliferation of the smooth endoplasmic reticulum corresponds to hyaline cytoplasmic inclusions seen under ihe light micro scope. Cytoplasmic Inclusions, consisting of con centric whorls of closely packed smooth mem branes, were noted in the mice. Additional findings were swelling of Kupffer's cells with an increased number of lysosomcs and vacuoles. Kimbrough el al.1,4 exposed rats to a diet of 20, 100. 500, 1.000 ppm of Arnclor 1254 and M CSC C'iiu tt H evitwt in bmirnnmrntel Cmutol 1260 for a period of H uroliths Increasing liver weight with increasing dosage was noted, hut was not statistically significant for female rats at 20 nr 100 ppm Arnclor 1260. In mate rats exposed lo Arnclor 1260. enlarged hepatucytes and inclusions in cytoplasm were commonly noted at all dosage levels; Increased lipid was noted m all rau ai 100 ppm and higher doses. The effect .was less maikrd in females, will) little sign of effects al 20 ppm. With Aroclni 1254. the findings were simitar except that adeunfihrosu wax marked at higher doses. Uliiaslrnctuiat changes consisted of an increase of the sinonlli endoplasmic reticulum and of atypical uriiochondtia. The epithelial com ponent of adciiofihiDSis consists offithlet cells and celts similar to llrnsc of the epithelium of the bile ducts. In a taler study these workers1*'''1 *4 studied ra< livers fur H months after exposure to 500 ppm Aruclor 1254 for 6 months. Liver weights decreased ovet this period from b.32% to 3.34% (control values .2.44 to 2.59%). Morpho logical clwngcs persisted over the recovery periud with small lipid vacuoles in the cytoplasm of liepalocytcx churirclcntiic of the recovery phase. Ademiftbrnsis was examined in more detail and was considered likely lo he a permanent lesion. The final residue levels io ihe liver range fmm 17.3 to 26.2 ppm after R mouths off dotage. Allen and Abiahamson** * exposed oils to a diet of 1,000 ppm nf Atoclor 124R, 1254. and 1262. Approximately threefold increase In liver weigh! was noted, with some incense with increasing chlorination. Tire morphological changes - proliferation ot ,i|rc smooth endo plasmic rcliculum, formation of large membranous concernrtc arrays and lipid droplets wilhin lire cytoplasm agree wills other workers. There was some indicnlitNt of decreased en/yme activity after six weeks as compared In four weeks, but the etianges were n( consistent from enzyme (o enzyme, nor were the changes marked. Hansel) -and Kctrhichou' ** have studied Ihe effect or a series or putc isomers, biphenyl, mono-, di-, tetra- and ociachloiobiphenyts, on the morphology of rat livers. They found (hat hiphenyl, mono, and dichlmnhiphcnyls caused hnte morphological change, (ml that the pure higher chlorinaicd isomers caused changes comparable with Atocjot 1254 and 1260. Tiros for this response to PCB's. tire pure isomers and commer cial mixtures act in the same manner. Litlerst cl al.1*' found no effect on liver weight at I' AlrX-lor *1 ir. 50 pplir, SI;' hut l 242..o' enlaigciocio Ill'll of I) , nienl -is l*"liver enlaigi' POls lh.,11 eir/vines II win k <m oHr LXijilnl no i been naml Peak,iII RNA in A i pplir Arocl. Mould he r1 of Ihe stiro. C. Hepatic i One ol clrlnriue o hepatic no-, examples f Burns.1'1'' Alvares enhanced systems s: Inc. clli' chrome 1' iiicliis, mg i cyclic hr. iiiixiinc. r coitrt'KinnJ propeihccychi I Aheiiui* propci in Buiik' eirli.ince<i ami liyji in'll agu llrat hyiii a grejIcT single rl> I signifu ir of livet Old* I'.omciK 1 cn/yntc I diflcicn: , caused t i Increasing liver noted. but wilt n.de rate it 20 or rats exposed it* i * ind inclusions -led it ill dotage mi all rats it 100 1 wot less maikcd `eels 11 20 ppm. let were similar uikcd it higher consisted of in me reliculum ind epithelial corn>f gtiblel cells and mliurn of the bile workers' '1,1 M .tfief exposure to months Livei *i1 from 6.J2% to 59%). Morphorecovery period he cytoplasm of < recovery phase, mole detail and permanent lesion. i tange from 17.3 iosage. vposed ols to a 1248, 1254, and i increase in liver re increase with e morphological Hr smooth endokuge membranous nplets within the orkers. There was 'vme activity after >< weeks, but the Mom enzyme to <.irked. have studitd the .. biphenyl, mono,, 'phenyls, cm the y Tound (hat bihcnyls caused little n the puie higher 'ranges comparable H. Thus foi this inert and commerinner. no effect on liver ! welgln at 0.5 or 5 ppm for 4 weeks willt any | Aroclor studied (1242. 1248. 1254 m 1260) At I 50 ppm, significant increases were found fur sill ' hut 1242, and at 500 ppm all ArtKlors caused liver erdargeincni. These workers also studied the indc(ion of hepatic eti/.ymes, finding some enhanceI men! as low as 0.5 ppm Hie conclusion is thi ! liver enlargement is a good deal less sensitive to j PCB's than the induction of some hepatic ; enzymes. This conclusion is in agreement wilh | work on other organochloiincs. . Detailed sludtes tin altcraiions ot the liver have j not been made outside those on mammals. Liucci ! and Peakall'** ntrled an increase of cytoplasmic i RNA in American kestrels exposed to a diet of 5 . ppm Aroclof 1254 or (260, an attention lltat - would be expected to correlate wilh proliferation of the smooth endoplasmic reticulum. C Hepalic Enzyme Induction One of the best siudied effccls of nrgann- chlorine compounds has been the induction of hepalic microsomal enzymes in mammals. Sec for examples reviews by Conney* ** and Conncy and j Bums,'* Alvares el I.'*' found that Arocloi 1254 enhanced the activity of all hepatic enzyme systems studied (viz,, henzo(a) pyrene hydroxy - lase, etltylnioiphinc N-dcmelliyla*c, and cyto chrome Pas#). In this regatd, PCIl's have the inducing properties of both barbiturates and poly cyclic hydrocarbons. Since Aroclor 1254 is a mixture, It it possible it cnnliins one or more compounds with barbiturate type inductive properties and one or more compounds of poly cyclic hydrocarbon class of inductors. Alternatively PCB's may possess the combined properties of the two classes of inductors. Bruckner el al.'** found that Aroclor 1242 enhanced the activity of both N-dcmethylution and hydroxylilian enzymes. The relative induc tion agrees with the findings of Alvares et al.1*1 that hydroxylitton enzyme activity it increased to a greater extent than Ndcmcthylalton activity. A single dose of 100 mg/kg was enough to cause significant Incicaae of enzyme activity and increase of liver weight. Chen et al.'41 studied the effect of (wo pure isomeric set rachl or obi phenyls (TCB) on hepatic enzyme systems. These workers found noticeable differences between tht effects of 2,2,4,5 TCB, caused enhanced enzyme activity of ethyl morn pltiuc N-demcthyl.isc and aniline hydroxylase nt Ivi'th male and female rats over Hie dove range 5 to 40 mg/kg daily lor 5 days With the .t,.t',5.S' isoinei enhanced, enzyme activity was tinted only fin the male rats, whetras significant decreases nf Cn/yme .n livily were noted fur female, liven with the males, peak activity of aniline hydinxsl.ne was noted at 5 mg/kg with small rtbiaucniicm at 20 and 40 mg/kg These findings indicate that studies of mcihanism nf indnciiitn may be difficult to evaiu.ile iT cinimtcisial tnixuncs of PCIVs aie used Johnstone cl al.14*1 studied the effects of pure hi phenyl and isnmciie.illy pure mono-, df, letra-. hCxa-. and octoclllmobiphcnyh (Hi ItcpaMc fi.nclinn in the rat. These woikets studied the billow ing hepatic en/ytnc system*: O-demeth) lisc, Ndcmcthyl.ise, aniline hydroxylase, nitroreductase, in addition to conjugation of hioinosullphihalein and iK'utohathital sleeping time. There wnc some variations from enzyme system to enzyme, hut in gcnetal, little nr tin cffccl was seen with |hc pure biphenyl, 4-timno-CI, 2,2',2,4'.2.5,2',S,1 whereas imikcd effects were seen wilh 4,4', and the three hcxachloio- and ime ocUtchhuoliiplienyls hictcases in enzyme induction paralleled closely decrease* in bailiilurate sleeping time. These woikers also found similar hepatic enzyme indue lion with the commercial mixtures, Atoeloe 1 254, and 12<<0. in thisc found wirh ihc pmc hexa- ami nctnshlotn isnmets. The marked effect of 4.4' corn pried with the nlhci low clitorn compounds shows the difficulty of evaluating icsuhs limn intxmres. Chen and DuBois' ** studied the effect of three difrcicnt Atnclors (l 221. 12S4, and 1260) on ihree hepatic enzymes (N-dcineiliylasc, niitophenyl pltosplionntliioaic detoxification, and Odcmctliylasc). hi all cases, the least chlorinated ITH (1221) was the weakest inducci. and In most cases no significant induction was observed. The most marked induction was Aroclor 1260 on N-dtmcihylase and Aroclor 1254 on Odctncthylasc. These workers also studied the dose response of Amclor 1260 end its interaction with DDT. They found significant increase nf the ini*s( sensitive cn/ytnc system (N dcnicibylasc) at a dietary level of I |i|tm Aroclor 12(r0 fm t week and the olhci systems wcic significatrlly elevated al this dietary level after J weeks. DDT -j! 5 ppm fm I week stimulated nil enzyme systems, and a diet containing DDT and l*CB showed additive effects on N-dctnetliylase, but not with Hie other 2 September 191$ 489 t enzyme systems. These workers also uuicd that malt mis were more sensitive Dun females end that young injles were more susceptible lo enzyme induction than adults. Liltersl et al.'*' studied the effect of four Atociors (1242, I24S, (254, and 12f*0)on several hepatic enzyme systems (uiirorcduclirm. demcihylation, and hydrnxylahon). In general, (he degree of enzyntc induction increased as cltiorinalion inn eased, and a dnsc-rclaled increase was found in all systems. Induction was seen al the lowest level examined, viz., 0.5 ppm for 4 weeks. The level of cytochrome Paso was less marked than the enzyme systems Bickers et al. *** found Hut Atoclor 1016 was a less potent inducer of hepatic eu/.ymt-s than 1254. Dosage was 25 mg/kg daily, intrapcrituneal. for 6 days. Hydroxylase activily was stimulated hy 1254 but not by 1016. Interestingly enough, hexobarbital sleeping time was significantly reduced by 1016(48 miu vs, 100min by controls) as well as by 1254 (24 min). N-dcinethylase activity and cytochrome P*# levels were increased by both Aroclors, ullhnugh the effect was much more marked with the higher chlorinated material. Li 11 erst and Van Loon1*4 examined the effectiveness of Aroclor 1254 as an inducing agent compared to two well-studied agents, DDT and phenobarbilal. They found that PCB's were far mure effective than phenobarbilal and at least as effective as DDT They found that 0.05 mg/kg/duy for 30 days was not effective, but that 0.05 mg/kg/day caused a significant increase in micro somal hydroxylation enzymes and cytochtome Pas*. Studies of hepatic enzyme induction in birds are a good deal less detailed titan ihoce on mammals. Risebiough et al." demonstrated (hat Aroclor 1262 al 20 mg/kg, itrlramuscular, caused increased metabolism of estradiol, and that this PCB was more active than either DDK or DDT ill causing induction of hepatic enzymes in the pigeon. Bailey and Bunyan'41 found that a diet of 500 ppm Aroclor 1242 increased both microsomal protein levels and, more markedly, cytochrome P,e levels. The microsomal protein levels returned lo connot values after two months, but cytochrome P, was still three times the control values six months after exposure to (he PCB had ceased. Nowicki end Norman'4* dosed chicks, starling al I week of age, with I mg Aroclor 1254 or I26D daily. They found cnluticcd metabolism of steroids and further noted that the effects of hntlt ArncWws were stmibt and also equivalent to p.p'-DDT and o.p'-DDT. Nd data arc available on (he (hteshoid levels of PCIl's mi hepatic enzyme induction in birds, hm ji is piohably not markedly different from that in mammals The only data on i'CB-induecd microsomal enzymes outside tnainmais iimlhttds appear lobe the wuik of Rhec ami Plapp"'1' on house flics. These workers studied (he eCteelx of Aroclor 1221, 1242. and 1254 and found increasing induction wiih incieasitig degree of chlorination. Tltey lound ttmt minute atnnimis, he., I Mg/jzt. caused measured indncilon and concluded that a nn-effccl level apparently does not exist. It likely tlwt this induction increases the ability of the insect to detoxify insecticide chemicals. Thus lire wide spread contamination of (lie environment with PCB's may be a factor in increasing the resistance of insects in insecticides. There is abundant evidence (hat PCB's are potent Inducers of hepatic microsomal enzymes. The enzyme systems studied have been mainly Itydinxylascs and N- and O-dcmcthylases. In genctal. the degree of induction increases as lire degree of chlorination increases. Threshold values as low as 0.5 ppin have been found,'*1 although other winkers'10''" love found the threshold dose between I and 10 ppm. lire minimum dose causing an effect should he compared with calculated intake to ascertain if an effect is likely, In Ihe ease of matt, lire normal exposure to PCB's (see Section 4) is too low for an cDcct (Mi hepatic enzymes in be observed. Only in lire case of accidental exposure, such as Ihe "Yusln" incident in Japan, would hepatic enzyme induction he expected lo occur in man. Under these conditions interactions with drugs would have lo he considered. Tltc residue levels discussed in Scclion 4 indicate that marine mammals and predatory birds are exposed to levels of PCB's capable of cuusing enzyme induction. Tlte next question to be answered is whether this induction is of importance to the runciiuu and survival of the aithnal. While the documcntalKHi of induced micro somal enzymes is extensive, the evaluation of it effects on the intact animal ate much less well studied, I he use of increased hepatic function to shorten barbiturate sleeping time is one technique, indeed tire field of hepatic enzyme induction by ; Chloiltl.ltcj | alterations ; cages oT in i ' ihckvi-, ct sICCpttlE tic I dotage or | al.'41 loin I lime with I cldori", sh, and iiuikii | itexa- and i' ] 50 mg/kg '< sleeping tin al,|v' fad 1254, ami I of rats cv!" to 250 da) Aroclor I 2 were tn.iK al."4 fortr Significant!' These stuJi largely slue ine teaemg compound at cimtpjia Tltctc 1 Shows l|) . hepatic ci h/.ing the I these situ unlike tin on cireut. tnechamvn ! Itsm of o I increased | lion of 1 I obi.nurd l PCB's 1 Viliem j in lire m 1 j eptandtoj oMOO 10 I 10 mg/kg 1 on the 1 ' slciotdc ' I Itl.tic rat increase t COlllljliil tccloMcn and rent, mouths 490 CftC Critical ft ericwi in tnnrtitimenlal Control HONS 20**68 ,,,ed metabolism <i the eMects of Imi ettuivi'nii to :mc available on hepatic tiuymt My noi markedly icrd microsomal nils sppear to be ` on house (lies, nf Afoctof 1221, casing induction non Tliey found Ug/jar, t*0*** ,1 that a no-effect ts likely that this <rf the insect m lhus the wideiiviionnscnt with -up the resistance ihat PCBs are ..sum-it enzymes. ,ve been mainly Icmethylates. In - inet eases at the Threshold values uid,'*1 although nJ ilie ihtethold i effect should be to ascertain if an mail, the notmal t ts too low fot an observed, Only in lie, such * the -t hepaiic enzyme . in man. Under nh drugs would uc levels discussed me mammals and i levels of PCB't action. The next iict this induction ii and survival of i induced micro evaluation of its i- niucti less well ,-patic function to - u one technique, yme induction by chlorinated hydrocarbons was discovered by . all era) runs in barbiturate sleeping times after the cages of rats had been treated with thlordane.111 Bickers el at.14' found marked alterations in sleeping time with Aroclor 1016 and 1254 at a . dosage of 25 tng/ky for fi days. Johnstone et tl,1 `3 found no effect on pentobarbital sleeping ` time with biphenyl, d-mono-chlmo, or 2,2 dictdoriv, slight decreases with 2,4' and 2,5,2',5`, and marked decreases with 4,4', 2.4.2',4` and 5 hexa- and octochloroisotncrs. The dosage level was SO mg/kg/day fur 3 days in rats. In some cases ' sleeping time was reduced by 00%. Viilcncuve et i a).113 studied (he effect of Amclors 1221, 1242, 1254, and 1260 on the pcntoharbilal sleeping time of rats exposed to dietary levels for 20 ppnt fur up ' to 350 days. Marked effecit were found only with | Aroclor 1254 and 1260; bolh of these compounds I were more effective than chloidane. Zcpp cl | id.114 found that 10 pptn Tor 12 weeks caused significantly shorter periods of sleep in rabbits. | These studies show that induced hepatic enzymes. I largely studied by in vitro methods, arc capable of increasing the metsboli/aliuti of a circulating compound enough to alter its physiological effect at comparatively low dosages of PCB't. 1 There is a considerable volume of wurk which I shows that a varteiy of organoddurines induce -[ hepatic enzymes which are capable of metubo> bring the naturally occurring steroids. Must of l these studies are on in vitro metabolism, aud | unlike the experiment using barbiturates, effects . cm circulating levels can Involve a feedback i mechanism. In the inlacl animal increased mclabo] litm of steroids could be compensated fur by increased synthesis of these agents. A considersI lion of this problem requires the use of data i obtained cm other chlorinated hydrocarbons than I PCB's. | Villeneuve el it.'11 demonstrated an increase in the urinary excretion of estrogen and dehydro- I epiandroslerone in the boar following a single dost of 100 mg/kg Aroclor 1254. Nu effect was seen at 10 mg/kg- While these experiments show an effect on the intact animal, the circulating levels of ' steroids were not measured. Recent studies on male rats fed toxsphene have shown a rapid I increase in enzyme levels, and a transient drop In circulating testosterone levels '14 The levels of j teslostctone returned tu normal within a few days I and remained ai normal levels over the nexi six j months although hepatic enzyme levels remained elevated. Orhcig and Lundbtrg'11 found tint DDT and PCB's were ahic to reduce the weight of testes and seminal vesicles of castrated rats, hut not of mlacl animals. In both castrated and intact animals, enhanced hepatic en/yint' indue turn was found and it was concluded that the intact animal was capable of compensating for enhanced Steroid breakdown, although nu direct measurements of steroid levels were made. In ring doves, IVakall'1* found that DDL caused enzyme induction, dccicatcd ciiculating levels of estradiol, and a slight delay in the onset of breeding. Studies of herring gulls, collected when incubation was almost complete, have shown no differences in blood Steroid levels in birds collected from take Ontario with high levels of K'B's and DDL and those collected in New Brunswick.11* Aeluat levels in eggs arc given in Section 4. The best summation is that hepaiic enzyme induction can cause a temporary decrease of circulating steroid levels. This may be reflected in delayed bleeding,'14-'4 but feedback mechan isms then come into play tu restore normal steroid levels. No overall effect on reproduction appears to be caused by this median inn. D. Mammalian Reproduction Villeneuve cl til.11* round no effect on icpn- ductlon in the rat at dosages of Aroclot 1254 up tu and including 100 mg/kg/day given orally. These workers examined the number of liners, average litter size, resorption sties, aveiagc liner weight and checked for anomalies. The only alteration seen was a slight reduction in litter weight and a alight increase or litter size at the highest dosage. Kcplinger et al.ia< studied the effects uf Aroclor 1242,1254, and 1260 on rats ai dosages or I. 10 and 100 ppm. The only effects noted were decreased survival of pups at 100 ppm uf 1242 and 1254 and decreased mating indices with 1242. In rabbit*, Villeneuve et al.nt found nu effects at dosages of 6.25 or 10 mg/kg/day, but at dosages of 12.5 to 50 mg/kg/day, fetotoxic effects were noted Abortions, maternal death, and siillhoins occurred, but no consistent skdcial abnormalities were foun , Since the work was dime by the same gtou , it is clear dial the rabbit is more sensitive Shots the til to Kill's. In 1968 and 1969 (he feeding of Coho salmon taken from like Michigan led to reproductive failure in intuk.111 In a latei study Rmgct el 1 t September 1975 491 I df P<'n \ nn Ff Pftviur(irrii i( t j f |i|c b lh ilifv a).1*1 found that I ppm of At odor 1254 caused a slight reduction In reproductive success (4.3 kos/ female compared to 6.0 In controls, statistical significance not staled); but a' 5 ppm Atoclor 1254, complete reproductive failure was found in | experiment, and only 0 8 kil/femate in anutliei experiment. Premature births in California Sea Lions have been associated with high organic chiorine residues."1 In this, no controlled experi mental data is available to verify Ihe relationship between premature pupping and orgarutchlonne residues. The levels of total DDT arc much higher than those of PCB's (see Tiblc 9), bui the levels of PCB's In the liver of females giving rise to premature pups is similar (5.7 ppm) to the values found In mink dying from eating Coho salmon (5.2 ppm). C. Avian Reproduction Eggshell thicknets - Decreased eggshell thickness caused by organochlorines, especially DDE, has attracted a good deal of attention (see review by Cooke'"4). In the case of PCB's, the bulk of the evidence shows that these compounds do not affect the thickness of eggshells. The following studies have been made: mallard and bobwhlle quail,1"" ring doves,'** chickens,"v,i* Japanese quail,'*" pheasant,'*' ..kestrel,'** and mallard.*** There is an early report by Keplinger et al.'*' which mentions eggshell thinning In chickens but docs not give specific data, and Call and Harrell'*4 found egphell thinning In Japanese Quail using three different Aroclors Egg production and haichablllty - The basic data are summarized In Table IS. The overall conclusion is that egg production it often reduced although the effect Is not very marked. In contrast, massive effects are seen on hatchablllly In most studies. In the chicken the threshold effect dosage is around 10 ppm. The depression of hatchabillty does not appear to be caused by lack of fertility. Briggs and Harris'** found that while 83% of the eggs from PC8-treated chickens were fertile, only 14.8% hatched. These found that comparatively little mortality occurred during the first six days of incubation, that (here was a striking increase over control values during the second week of incubation, with considerable mortality in Ihe third week although control values were also higher Tor this last period Plalunow and Reinhart'** also found nn effect on fertility, although hmchability was reduced to 'most wo at the highn dosage of PCB's Tlitu workers timed tlut initially embryonic mortality occurred at the latter stage of development, hut shifted cortier as the experiment progiessed It is likely that this was due to increasing levels of PCB's in Ihe eggs a* the experiment progressed. Lined and Peakall1* found an essentially linear increase in residue levels In eggs of ring doves exposed let |0 ppm PCB's for approximately )00 days when the increase began to reach a plateau. Lillie cl al..*"* studying six different Arodtus. found iki effect on fertility, and that most of the death* of cinhryos occurred os. (he SOih and 21st days of incubation, Dahlgroi end Lindcf,1*1 in their studies un Ihe pheasant, found a significant Increase in egp that pipped but (ailed to hatch. Scotl et al.**1 found that halchabltity was reduced to about 72% of normal when the residue level in eggs was 2.2 ppm (wet weight). At 3 ppm hatchabltity Is down to 56% and with 4.5 ppm or more PCB hatchahility is close to zero. Platonow and Reinhart1** found that halchabiltly was not affected when PCB concentrations in eggs were less titan 5 ppm, but that IS ppm or more caused Ihe majority of embryos to die. Tuoiasouis et al.'** found that yolk levels of under 10 to 15 ppm have no adverse influence on embryo development in the chicken. The most detailed study of the residue levels causing embryonic mortality are those of Britton and Huston'** (sec Table 16). These workers expressed their results based on the weight of the yolk, whereas Scott er al.'** and Platonow and Rcinhait'** apparently used whole eggs for homogenization. Since the PCB's are concentrated in the yolk, using the yolk will give higher but more meaningful values. Different Aroclors were used In these studies: Britton and Huston1** used 1242; Scott el al.'"1 used 1248, while Platonow and Reinhart1"* and Tumasonis et il.1** used 1254. Carlson and Duby'** injected Aroclors 1242, 1254, and 1260 into fertile chicken eggs. They found Increased emhryunk mortality with 1242 al S ppm with almost complete failure at 10 ppm. Aroclor 1254 showed some decrease at 5 ppm and marked decrease al 10 ppm, while 1260 was not effective In causing .mbryonic mortality al the highest dose. viz.. 10 ppui. These results parallel those of Lillie cl al.*** who found that 124* and 1248 caused a much larger decrease of loichabilily than Aroclors with either high nr lower chlorine j ; | I I : 'j I 1 ! | i I j ] ; j I I IJ j i I 1 | , > ' ! , ( * , < 4tJ C#fC CWfic#/ H rvitwt in tinvironmenttl Control HONS 206870 I Ly was induced lo j ipe of POH's. These J inhrynnii mortality I .< development, bur ] tut pmjictsed li is increasing levels of i<erirnenl progressed, an esteniijlly linear 1 ejtjp of ring doves 1 approximately 100 'i lo reach a plateau, different AiouluH, ltd that most of the <it the 20th and 21st i and Linder,'*' jn 1. found a significant n failed to hatch, oil hilchabilily was nul when the residue I weight) At 3 ppm .tnd with 4.5 ppm or re lo zero. Plalonow hntchabilily was not o.ins in eggs were less i or more caused the Tutnasoms el el.1** r 10 In IS ppm have iryo development in railed study of the vonic mortality are "* (see Table 16). i results based on (he Scull et al."' and ^patently used whole nnce the PCB's are ng the yolk will give dues. 'vcd in these studies; !242;Scott et al.1*1 ntd Reinhail "* and 12S4 Carlson and '242, I 254. and 1260 licy found increased '242 at 5 ppm with 1 r ppm. A rutlot 1254 s |)pni and marked '(0 wi. nm effective i.ilny .. me highest .tills pa.. .`I those of ihat 124 2 and I24R <: of hauhabtltty than i or I'" chlorine < t- 1 ** I z su J I x i? II i n\ 3 2<V uO* "m * - * 1? O* S* 3^ -l S 11 * I E; iliia iI~*s **;f 2 *il o i g ^s;^ >^22 E S 1 e Hitt c .* 5V 5V 5tl 5V5V zOzOOz OzQz tV % 2 E*4 (N n^4 aN tM ^4 rj oK *N 1 1 1 3 3 n ! i st snt KS ed e8 |l n 15 :1 lO 53 o IM M O SS st g 22 K a *? Ps |* "^, s *oo ii E*4 IN It1 i\ *s Kill -- m Q M E & o E|EE lalsa ."S?S5 EE as gg il II *> e lilllh IH O 8.s0i*- 6sr*lol iH l September |*U 4V) CRC C ritic il R evtewt in fin n ro m n rn ltl Control I TABLE 15 (continued) Effect! nCPCR'l hn Eg fteduction and Hatcfcabdity Specie! Bobwhite quail Maltard Dotage 30 ppm 23 ppm 40 ppm Ring do*e 10 ppm *N" effect it t ppm. **No -fleet at 2 ppm. Egg production 2 teatoot 1234 No effect 2 taatont 4 monthl 1234 1234 No effect Decreased on diet which alio contaitied DDE ) nontht No effect Hatelability No effect No effect Not studied Markedly reduced Reference Heath etal.'** HeathetaL'*' Risrbrough and Ande^Ksn,, Peakat and ftakal!' * * TABLE 16 MatckatsBty and Rendue Ltnh in Egp of Ohxtm Espond to Arodoc 1242 Dotage (Arodor 1242. ppm) Wetki on dmaac l2 3 4 3 6 to Decrease in halchabilisy av. ns SL as 81 167 Reiidue in yolk 0.3 0.1 1.2 1.6 23 3.7 20 Decrease in hatctubiiiv SI 3<n 26* SOI 101 447 Residue in yoik 1.1 2.4 2.9 14 4.8 6.2 40 Decrease in hatchability SI 741 911 977 m 1007 Reiidue in yolk 24 4 6 34 SB 6.7 7.7 BO Decrease in hatehabiliiy 11 1001 1007 1007 too? 1097 Reiidue in yolk 2.9 5 6 12.3 173 21.8 27.3 ni - Not sfitifcanL Adapted from Britton. W M and Huston. T. H.ItoWr. Set.. 52. 1620. 192}. HONS Z0687Z 3 X. ft < a. >T5 ? ^ e"o * o<C: 3 n r' 3C ^ CX a C* ' v ys ?P *5 rj- > <n> d_O A-7 --fC-, o<A " C -t " s^ o< o W. M. and Hnnon. T. M.. I W r S ri. S I. 1610. 197 V cuntcnl Carlton and Duby1** found that most mortality caused by Aroclor I 242 was ai (lie early stage of "development, in contract wifit innsi studies of the clTccl or diclary Arnclors. These workers alsti tvolcd lhal growth was retarded in Ihc chicks that did hatch after exposure to 12*2 in lire cue, whereas these elTecls were not noted Tor 1260. The studies of Heath el al.1** on bnbwhiie quail and mallard arc in marked contras! lo those on the chicken, in the taller species it is clear thi a dietary level of ID lo 20 ppm for a few weeks and residue levels of 5 lo IS ppm are enough lo cause severe etnhryonic mortality. In Heath's wmk no effects were seen even after the birds had been on dose for IM years, and residue levels oT two Mallard eggs were 33 and $6 ppm (wel weight). Effects on males - Platonow and Funncll**' fed cockerels Aroclor 1254 as a dietary level of 250 ppin. A marked reduction In comb size was noted within six weeks, and Ihc weight oT Ihc lestes was reduced a Tier nine weeks. No direct studies or the reproductive performance of these birds were made. Lillie el al.** fed cockerels Aroclor 1248 al 10 and 20 ppm for an 8>wcck period without finding any effect on semen or fertility. Teratogenic effects - Carlson and Duby'** Tound that 5 ppm of Aroclor 1242 injected al day 0 caused several malformations, viz., development or only one eye, hydrocephalus, incomplete abdominal closure, and nervous tremors. Tumaionii et al.1** noted leg, toe, and neck deformities in many chicks that hatched from eggs wilh a yolk level of 10 to 15 ppm Aroclor 1254 or more, Cecil al al.** examined the elTect of a diet 1 of 20 ppm of a range of Aruclors on the t production of abnormal embryos. These workers | found a marked increase of abnormal embryos as a ' percentage of fertile eggs for Aroclor 1242 and j 1248, a slight effect wilh Aroclor 1232 and 1254, j and no effect for Aroclor 1221 and 1268. In all , the treated groups, there were 843 dead embryos of which 286 were abnormal. The commonest abnormality was edema including edematous cysts and subcutaneous edema. Other abnormalities, in i decreasing ord.r of occurrence, were unabsmbed yolk, small body, external hemorrhage, skinny rolaled ankle, and deformed beaks. Dahlgren and Under'*' noted decreased chick weight in their studies on the pheasant, hut no mention it made of abnormalities Peaknll et til. '0 ^ found an met ease in chtoinosumal almoitrvilitics in embryos of rtng doves exposed to 10 ppm Aroclor 1254. An interesting contrast can be made between the errevis of KTt's and DDli on avian rcpioductiou Ibis differentisiiion is ot some itnpoi lance lo wildlife loxjcoli>gisls since both compounds ale found together in bird eggs, and hc cffecls oT oigannchlorincs arc widely considered to have had adverse effects on some avian populations In ihor discussion of differing elfccls or PCB's and DDL on avian reproduction, Pc-ikill and Pcakall1** considered Ihc effects under three headings. vi/_. effects on the eggshell, effect of iceldurs to ihc egg tut Ihc embryo, and elfevt on percmil behavior. F. Direct Estrogenic Effect* Tire geometric similarity of DtJT and PCB's to the synthetic estrogen, stilbeslrol. has led to the examination of Ihc possibility that chlorinated hydmcarhoiis could act as synthetic estrogens10* These workers examined the effect or uvei 50 compounds no the glycogen response of Ihc rat uterus. Tliey Tound lhal Amelins 1221. 1232. and 1242 had a minimum effective dose or 8 ing/rai and that Aloelots 1254 to 1268 were inactive. In contrasi, the minimum effective dose nT dietDyL tlilhestrul is 0.1 pg. or a factor nf nearly 100,000. Aroclors are weak estrogenic agents, but the value of 8 ing/rat should be compared to environmental levels ralhcr limit to 0.1 pg/ral of diethyl- stilbeslrol. On a mg/kg basis. Hie minimum effect dose of *n Aroclor in Bitman el al.'s1*0 ccpeiiments was 160 mg/kg. No residue levels m the uterus were measuiad, but the dosage suggests that Ihc levels would be high by environmenial standards. Nelson** examined the effccis of scvnal organnchlurincs on the bindingoflabclcd estradiol on the rat uletine receplor. The effects of the organnehlorines were compared to Ihosc of dicihylslllbesirol, making possible direct eoinpan. son wilh the experiment of Bilman el al.'s'** Nelson found that dielhylslilhestrol was effective in causing SO**1 inhibition oT eslradiol binding at an in vitro concentration of 0.2 pph. The most active uigaiiochl urine (o.p'.DI)T) required a tonccnirotion of 0.6 ppm lo produce 507 inhibition. Oihei organochlorines requited 10 lo 100 ppin m cause (his degree of inhibition, wilh Aroclor 1221 being more active than 1254. While ciiiical in vivo experiments have not been carried out. Hie data Stt'lcnihii 197 S 49j , i > . . < ' ; - ` f' l ! j i ' 1 < . ' . < : ' Adpl(4 from n v - Not gniricnl HONS 206873 piesenlly availahlc indicate Hut serious effects will nut occur >l environment*! levels. C. Thyroid Function Jefferies and Partlow** dosed lesser black- hacked gulls with Aniclor I 2 54 at SO. 100. 200. and 400 ni|/kg/day for 8 weeks. An increase in thyroid weights (30 mg to 40 mg) was noted between the controls and dosed birds, but no dole-dependent increase was observed. Aiviiysi* of the colloid area showed a small increase. Histo logical changes were diffcrenl from those observed with DDT.10' DDT caused colloid loss and hypcrirlasia, whereas PCB caused larger follicles well Tilled wilh colloid. Hurti cl af.*1* studied the effect of Aroclor 1260 ai 5. SO, and SOU ppm for I to 4 months on hobwhile quail. Significantly different thyroid weights were found for all dose levels af'icr four mouths, but (his effect appears to be due to the abnormally low control value fur this period. There was no actual rise in Ihyruid weights when compared to measurements made at one, two, ind three months. There was a tendency for I'*' uptake fo> the total thyroid to be higher in quail exposed to the highest dose ($00 ppm), bui this increase was significant for only one-time period and did not ihuw up when expressed on per milogram of thyroid bash. Curreui evidence does not suggest lhai PCB exerts an important influence on Ihyroid function. H. Vitamin A Cecil el al'* sludied the effect rtf 100 ppm DDT or 100 ppm Aroclor 1242 on lives viiamitt A levels in quail and rats. After 2 months on the diet, Aroclor 1242 caused a marked reduction (approxi mately halved) in vitamin A in male quail, but the females wcic unaffected. DDT caused some reduc tion, but this was less marked. In mis (lie levels were reduced to apptoxiinaiely half the control values by both compounds In both sexes. No symptoms of vitamin A deficiency were noted In either species. Studies on mammab at lower doses would be desirable in view of recent findings suggesting a link between low vitamin A levels and induction of cancer.*11 Jefferies and French.*'* studying the effeci of DDT on pigeons, found a marked increase in liver vitamin A levels at lower dosages (3 mg/kg/day and 36 mg/kg/day) whereas at a higher dose (54 mg/kg/day), there was a marked decrease from control values. Comparable studies wilh PCB`t are not available. I. Carcinogenic Effects ' Studies on I hit topic appear lobe very limited. Kimnri and lluha*1* rqmrled benign neoplastic lesions in the livers of all female rats which received mine than 1,200 mg of Kancchlor-400. but nn effect was seen on males. Nagasaki et ai.*1* reported dial 7 otil of 12 mice exposed to a did crmluining $00 ppm K-tncchlor-500 had luliiois of the liver, wheic hepatoma* were not seen at 250 ppm. nor with Kanechlor-400 and Kanechlor-JQO. llchiyuina cl ah*' * found that Kancclilur-4tK) was not a co-carcinogcn with mcihylcholanlhicnc at either 10 or 100 ppm. A positive cocarcinngenic effect was wen wilh DDT ai 100 ppm. Both of the direct studies on carcinogenic effects were carried out on a small number of animals for a single generation. While there is not any evidence of a strong carcinogenic effect, detailed, inutligencralion studies arc desirable. Green el al.* '* found nn cytogenetic effects on bone marrow and spermaiogonial eelb of rats treaicd with Aroclor 1242 and 1254. Doses of Aroclor 1242 were single doses of 1,250, 2,500, or 5,000 mg/kg, or mulfipic doses of 500 mg/kg, Aroclor 1254 was given In multiple doses from 75 to 300 mg/kg/day. These workers found no inhibition of mil ode division nor chromosomal abnormalities. These authors point out lhai their work docs not exclude the possibility Dial poim inuiaiinirt occurred, bui state that it it very rare for this to occur in the absence of chromosomal aberration*. ` i 1 1 1 ( i i ' i ' 1 ( ; i ' ' ( j i J. Immunosuppressive Activity of PCB'i Friend and Trainer*" examined the effeci of Aroclor 1254 chi mortality of young mallards exposed to dnek hepaiili* virus. Three dote levels were used, vi/,. 25, 50, and 100 ppm, in the diet. At all dosages, the mortality was increased mnrkodly over control values, but the greatest increase was al 50 ppm. The actual values were control 14,3%, 25 ppm 35.0%-, 50 ppm 65%. and 100 ppm 44.4%. Vi* and de Roij*'* studied the effect of 10 and 50 ppm Aroclor 1260 on the humoral Immune responses of guinea pigs. Tetanus toxoid injections increased the 7-glohiilin levels in coni ml animals, whereas ihis increase was not found in animals fed 10 ppm PCB. However, the animals exposed to 50 ppm did not vary signifi cantly from the controls. A significantly reduced number of 7-globulin-containing cells in the lymph | i | . I 1 , \ I j nodes wetc Vtniuljlr! lympii in-it group-. lr- cell-nifdi.ii 1 Af(>clof I.' foil'Hl rti:o iinill<|ni".ii| and cell-mr weie sa ri lo be loi- 1 out. Kolh-t Aioclors I slixn.icll n ircatmeui* neutralism than *\t' ! diffidence Arnclors decreased other gion Tlie nn ililinuliris! evaluate 1 ptoblcm. annlhff ` and olhri dhilily ti> K. Hydrin Met nn when cln wiili uiiti;' lhai Anv dotjges 1 siud> "iel at.*" and in tli pnmnuiiL for 3 m ppm. Rel chickens Aroclor 50 lo I1 gcnciali/ inio tin- tissues, a Bayer I he epic, to a dir fuond t) 496 CKC Office/ Reviews /it tnvirmtmrniel Control HONS 20*874 ' I I 1 lie very limited, nign neoplastic ..ile rait which kanechJoi-400, I. Nagasaki et ice exposed io a 'vhloi-SOO had iinmas were not cchlor-400 and ;' * found that .ncinogen with in 100 ppm. A ; seen with DDT icci studies on I out on a small enerailon. While ung citcinogenic m studies are eneiic effects on iul cells of rats 1254. Doses of i 1.250, 2,500, or < of 500 mg/kg. H.- dotes from 75 ikers found no -or chromosomal int out that their -ihiliiy that point h.it it is very rare - of chromosomal .f PCB's nned the effect of -f young mallards Three dose levels ppm, in the diet, 'y was increased but the greatest actual values were 50 ppm 65%, and tnii1" studied the .clor 1260 on the nines pigs "ctanus rglobul'', levels in increase was not l*CB. However, the id not vary tignifienificantly reduced it cells in ihe lymph nodes were noted in Ihc 10 ppm telanus toxoidstimulated group and in the unstimulatcd left lymph nodes of the ttiinuincd 10 and 50 ppm groups. In a subsequent pa pet Vus and l>ticl Grooienltuit1'* examined both (he humoral and cell-mediated immunity under the influence of Aroclor t260 and Cltiphen Af>0 These workers found that PCB's ai the level of 50 ppm had immunosuppresive activity of hnth the humoral and ccll-mcdialcd iminunlly. No significant effects were seen at tO ppm and (lie 250 pptn diet proved to be loo toxic for these experiments to be catricd out. Kn'.icj and Thigpen110 dosed rabbi's wiih Atoclors 1221, 1242, and t245 150 mg/kg hy stomach tube weekly for 14 weeks. All Aroclur treatments resulted in significantly tower scrum neutralizing antibody tilers to pseudo-rabies virus than was found in the controls. There was little difference between the affects of the three Aroclors. Total serum -y-globulin concentrations decreased with Aroclor 1242, but increased for other groups, including controls. , The importance of Ihe effects of PCB'i on the Immuuosuppresive mechanisms are hard to evaluate. The tack of dear dose dependence is one problem, and interrelation with other tticsses is another. The possibility of the burden of PCB'i and other orpnochlor tries* *1 increasing suscep- tibility to disease should be borne in mind. K. Hydropericardium and Generalised Edema , McCune et at111 discovered hydropeiicaidium when chickens were placed in a battery treated with unhardened paint. Additional studies revealed that Aroclor 1242 caused hydropericardhtm at dotages of 200 ppm and above. A more detailed study was made, using the same Aroclor, by Flick et al.111 Edema formation in the pericardial sac | and in the abdominal and subcutaneous areas was 1 pronounced in the chickens exposed to 400 pptn ' for 3 weeks, bul was much lets marked at 200 1 ppm. Rehfeld et al.**4 observed general edema in chickens when the diet contained over 20 ppm i Aroclor 1254. Chicks exposed to diets containing SO to 150 ppm to Aroclor 1254 had extensive generalized edema. This included serious effusion into the pcricardisl tecs, muscles, subcutaneous tissues, and abdominal cavtiy. - Bayer and Bird1** studied structural changes In the epicardium of chickens exposed for II weeks * io a diet containing 20 ppm Aroclur 1254. They | found that all the birds exposed lo PCB showed t i morphological changes in the pericardium and three oui of four birds showed large quantities of ascites fluid. Residue levels were not given, but the diet levels would suggest dial the levels would not be much higher than those of fish-cat mg birds from In gld y con lamina ted areas Vos and Kncman*** studied the cffecls of 400 ppm of J different preparations of PCB's containing r-OTchlorine. These were PIiciukIot DP6, Clophcn A60, and Arochir 1260. The chickens were exposed to lliii diet for 60 days. Hydiopcricardiuin was common In the Plicunclor and Clophcn group, bul rare and statistically non significant In the Arndt* group. Sunilaily abdominal and subcutaneou edema was observed only in the flrxt two pmtpe- These diflcrcttces were considered lo be due In the presence of chlorinated diben/ufurant in the first two preparations.*11 Nevertheless, there are con siderable differences between Vos and Kocinan's results on Aroclors and those of other workers. These differences tnay be due to the fact other workers have used lower chlorinated Aroclors (1242 and 1254) which may themselves act differently <n may contain more chlorinated dibenrofurant than Aroclor 1260. Firestone*1* reviewed the etiology of chick edema disease and concluded that the chlorinated dioxins and furans were the chemical agents responsible. In view of Hie studies of Rclifeld et al.114 and those of Bayer and Bird11* which show effects at modcrjic levels, viz., 20 ppm, it would be useful to examine the effect of pure PCB's to clear up the question of the agent causing chick edema. Recently hydiopcricardiuin end edema have been found In Herring Gull (farms wgentatu*) chicks from the most contaminated ateas of the Great Lakes.*-** In this case substantial levels of PCB's, DDE, mirex hexachlorobenztne dieldrin. and HCB were present. Bowes et al.*** were noi able to delect any chlorinated dibenzofuran or dibenzodioxin compounds in gull eggs from the Great Lakes. L Porphyria In contrast to their findings on edema, Vos and Koeman114 found (hat porphyria was induced by all preparations of PCB's studied. They found that the chickens increased fecal excretion of copmpmphyrin and protoporphyrin and fluorescence (indicating Ihe presence of porphyrins) in the liver, bile, smell intestine, and bone. Subsequently, these September 1975 497 workers11' nuide a more detailed *tudy using Japanese quail. Using Arocior 1260 il 50.' 100 250, and 500 ppm In Ihe diet for 7 day* on male quail they dctnortsintlcd a tenfold increase of mitochondrial -itntnolcvuliiik icid *yihciasc in the liver of bird* receiving 50 ppm, and a further increase at higher level*. Increased fluorescence of the liver only became marked at higher dosage*. Lower levels were studied on female quail. A slightly hut statistically nonsignificant Increase of t-aminolevulinic acid synthetase was noted at a dosage of 0.1 mg/kg/day for 7 days, but ihc increase was titpiificanl at a dosage of I mg/kg Aminolevulinic acid synlhelase calalyMs (ALA synthetase) the Tmi step In porphyrin synthesis, viz., the reaclion of sucdnyl Co A with glycine to form n-amino-0-kepioadtpic add. Metabolic control of porphyrin formation is excreted thiough i feedback mechanism ope rating n the first two steps of ihe pathway, viz,, ALA syn thetase and fi-iminnlevulinic acid dehydrase. ALA is also ihe precursor of the porphyrin moiety of chlorophyll and of the corrin ring of vitamin Bt *. The finding thal ALA synthetase is stimulated by tow levels of PCB's raises the possibility of a heallh hazard to persons suffering from aculc. intermillenl porphyria. Barbiturates, which also stimulate ALA synlhetase, can cause a severe attack of this disorder which can result in paralysis and death.111 Studies on herring guli eggs collected from contaminaied areas of the Great Lakes have shown markedly raised porphyria levels in the livers of embryo* compared to those from leu con taminated areas.13* M. Inhibition of Adenosine Triphosphatase (ATPases) by PCB's The effects of PCB's on ATPases and the possible role of inhibition of these enzymes on osmoregulation in fish have been examined by a number of workers Yep et al.111 examined the effect of Arodor 1221, 1254, and 126B on the in vitro inhibition of Na'K*-ATPase and Mg**ATPatct from several tiuues of Blue Gill fish. Overall. Aroclor 1254 was the most effective inhibitor, and Na*K*- ATPasc was inhibited to a greater extent than Mg**-ATPasc. Substantial inhibition was found at levels at low as 0.03 ppm in brain md muscle. In a subsequent paper,314 these workers examined the effects of Arudurs on both oligoraycinaciuitive and niigoinyciir- insensitive Mg"-ATPasc. They found that the olrgtnnycrivinserts!live M^' ' ATPase was inhibited a good deal more sirnttgly than the edipomycin sensitive Mg** ATPasc. Olrgomyciivsentitive Mg**-ATPasc is Involved in ihe rnltin-hondTia synthesis of ATP, whereas the physiological func tion of oligomycin-ittscnstltvc Mg**-ATPase is un certain In another paper,111 this group.compiled ihc inhibition of Ihrsc llucc ATPases Hi tissues of fai head minnows exposed lo Aroclor 1242 and ' 1254 for four months. Tliesc in vivo studies failed to confirm that ohgotnycin-insentliive Mg**- ATPasc was Ihc most slrongly inhibited, and results were erratic with enhanced activity seen in some cases and a lack of cleat do*c<activtiy relationship ' Kmicr el al.11* examined the effect of both DDT and Atoclor 1221 on both in vivo and in vitro ATPase activity and on osmoregulation in tcleosi fish and eels. They found that boih DDT and Aroclor 1221 caused inhibition of ATPase and decreased Ihe ability of both killifish and eels to osmoregulalc. The level of Aroclor 1221 required lo cause an effccl was much higher than DDT, in general uhoui two orders of magnitude. Davis et al,111 determined the dcgice of inhibition of ATPase in imui gill microsomes by Aroclor 1242 and 1254. They found that 1242 caused gieaicr inhibition than 1254. l-'ot bolli Arociors. 40 ppm caused significant inhibition whereas 4 ppin was not effective except <m Mg**< ATPase. Sharp el al.11* examined Ihe effect stf Aroclor 1221 and 1254 on Na*K* ATPases from beef brain and rabbi! kidney. They found thal 10 ppm of Atoclor 1254 and 1$ ppm of Aroclor 1221 caused slightly more than 50% inhibition. These workers found (hat phosphalidylserine and phos- phalidylinosllol protected the ATPasc from inhibiiiott and concluded tltat the phospholipids are necessary fur stabilization of the enzyme and that chlorinaled hydrocarbons interfere with the stabilization process. N. Physiological Effects of PCS'* on Micro organisms Keit el al.11* exposed the marine diatom. Cylimlntfhtro donicriiim, to Aroclor 1242 at 0.01 and 0.1 pptn. They found that harvest weight, chlorophyll index, and RNA levels were signifi cantly reduced at the higher concentration. The final PCI! level was PHI pptn. showing a concent ra tion factor of I.000.14* Similar concentrating I factors wen I SvriixsMii. I Mnsser c! i j on two man" tWh species ol ' diatom {TImI.i 1 25 pph bin . ! (Sktleiotuiwt 1 extent ai to p water atjyr i inp no tnhiln, slight cffcd. workers1*5 < spcercs com| diatom amt iwere iti Itnprevious p\(t. J (Punebcllu PCB-senxim. [ mixture wa, more surpu-I >agc was cl. i much lower ' cause inhthi- coricentratu , ppb, bui v i lowest t.vi, I hold valu-1 t have uni it i iuleracioK, i laminants studied l>\ ' interaction I growth ol I Nciihcr Hi t DDL tjti'i 1 in cumhm 1 cells hnl i. 50 pph I'l p of grtm-il countcraii 1 between l> Luard3 the sc ns 11 1254. Sin 0.1 ppti. ' to cause Uplake 1 scnsitivm . atcas to I' M-'oi o Arodm CRC Critical Reviews in Environment*! Control lound ihjl Ihe ivc was inhibited ihe uiigomycineurnyeinsrnsilivc 'k mitochondria l>ysiolpcal fune li:*'-ATPase is un - group Compared in tissues of Viuclor 1142 and vivo studies failed insensitive Mg**v inhibiied, and d aciiviiy seen in tear dusc-activity he effect of bofh 'Hi in vivn and in 'Mnnregulation in >id ihai both DDT um of ATPasc and tUifnh and eels to lor 1221 required vltrr than DDT, in ipniludc. Davis et of inhibilion of by Aroclor 1242 '42 caused greater Aroclors, 40 ppm lirreas 4 ppm was I'iise. effecl of Aroclor es from beef brain d Ihai 10 ppm of nclor 1221 caused ton. These workers :rine and phostic ATPise from the phospholipids >'f ihe enzyme and mlerfere with the PCB'a on Micra lie marine diatom, metor 1242 ai 0.01 mi harvest weight, levels weie signifienneentmion The 'vowing a concenha milar concentrating factors were replica led by Sodcrgren and Svcnssnn.140 Mosser ct al.*41 examined rite effecl of PCD'* uri two marine diatoms, a marine green algae and two species of fresh water gveen algae, One marine diatom {Tltolauimira pmnlotiaiw) was inhibited al 25 ppb hut not al 10 ppb, whereas lln- oilier {SkctcUtnrrua crMfff/woi) was inlvibiicd to some extent < 10 ppb. Ily cotitrasi (lie inaiinc and fresh water algae were much more resistant, one show ing no inhibition al 1.000 ppb, and others only slight effects at 100 ppb. Subsequently, these workers*41 examined Ihe effeeis of PCB'* on Ihe species composition of mixed cultures of a marine diatom and marine Breen nlgac. The results found were in line wilh those predicted from the previous experiments, viz., thai the resistant algae (Dumliella larii/tlecia) was favored over the PCB-sensitive diatom (T. /acoJornwie) when the mixture was exposed to PCB (Aroclor 1254) A more surprising resuli was that compel itiveadvan tage was clearly demonstrated al concenlraiiuns much lower than the PCB concentration needed lo cause inhibition of the pure culture. The minimum concentration needed to inhibit the dialom was 25 ppb, but selective advantage was found it the lowest conccnlral ion used, viz,, 1 ppb. The thres hold value for effects on competitive advantage have not been worked out. The complexities of interactions of various environmental con taminants on microorganisms have also been studied by this group.141 They found interesting interact ions between DDE, DDT, and PC IV s on tlw growth of a marine diatom (T. psttn/otiami). Neither 10 ppb PCB't (Aroclor 1254) nor 100 pph DDE caused significant inhibition of growth, but in combination growth was reduced from 6 X 10* cells/ml to 1 X 10* cells/ml A concentration of 50 ppb PCB's caused almost complete inhibit it hi of growth, but ihts Inhibition was markedly counteracted by 500 ppb DDT. Interaction between DDT and DDE was slight. Luard*44 also found considerable variation nf the sensitivity of two algal species to Aroclor 1254. She found Ihai Dunatidla was sensitive al 0.1 ppb, whereas Sccnrdcumn required 100 pph to cause significant Inhibition of radiocarbon uptake. Fisher el al,*4t demonstrated variahlc sensitivity of phytoplankton collected in various areas to PCB's. Moore and Harms144 measured the effect of Aiuclor 1242 and 1254 on iti srfu radiocarbon uptake by iinoinc phytoplankton communities from ihe iioiihem Gulf of Mexico Both An>j<><s showed etircls on ihe radiocarbon uptake ji I io 2 pph and I lie I.Csu values were (i.S pph and 15 pph, respectively, Moore and Harris**41 have examined Ihe efleei of Aroclor 1242 on net- and nannopbnkion. llnhitler being defined as Ihai which is tvol relaiocd hy a 20 lo HO pin net. They found Ihai nannoplankioir radiocaiboo uptake, winch accounted for almost Once quartets of tUr tola! carbon fi.vnien, was uuatlccicd by Arnckn |'42 al ill or 25 pph In conirasl, nei-planklon uptake was reduced hy 56',' by 10 pph and SK'Trhy 25 pph. Given the high concent rat inn factors fn-m water to microorganisms. It is likely (hji (Tit s entering the oceans via aerial Iranspmt wit) he rapidty taken up by marine phytoplankton More detailed studies arc needed to demunciraic whether or no! a teiious environmental effect is occurring. Studies showing marked effects on competitive advantages al I ppb indicate Ihai the possibility that PCB's could allci species composi tion need to be taken seriously. O. Effects of PCB's on Nonhuman Primates Experiments mi nnnhutnan primates are useful In the extrapolation of data from cvpcriincni.il animals to man. Allen e| al.*4* led iliesus monkeys diets containing 300 ppm of Anilor 124H lot `K) days. There was a gradual loss of body weight in most of the animals receiving PCB's The animals developed alopecia, acncfcmti lesions of tire skin, subcutaneous edema, and hypertrophy of the liver and gastric mucosa. In general, tire tespouses were similar to those reported in the "Yuiho" outbreaks in Japan.**'** Alterations to the liver weie similar to those repot led lot utbei experimental animals (Section SB) hi another experiment tin* group*4* examined the ahsorplion, distribution, and excretion of Arocli* 124,s in ihe rhesus monkey. They found lh.it uvet oocv of Ihe PCB was ahsorbed from the gastrointestinal tract, and that elimination from the body was slow. The experimental animals had slight bui significant decreases in hemoglobin and hcmatnciit. Lesions of the gastric mucosa woe considered lo be unique lo primates and this facet of the work was examined in another paper hy tins group.**0 The diclary concentration was the same as in picvious expetimems It was found that the liyperlmphjc gastric mucosa was scvciat limes Seplrmbii 1475 444 thicker than the control mucosa and consisted of (really elongated hyperplastic (lands coni lining mucus-sectcling cells. The authors consider rhat these findings are suggestive of an eventual neo plastic transformation. Additional experiments with lower dosages and long time periods will be necessary to assess the importance of these changes. The levels in these experiments arc high by normal food standards (see Section 4E>. Additional experiments by Abrahamson and Allen1 *' have demonstrated that the infant rhesus monkey is more resistant to PCB's than adults. No studies covering reproduc tion in nonhuman primates have been reported. 6. EVALUATION OF THE ECOLOGICAL SIGNIFICANCE OF PCB's While this is an attempt to assess lltc evidence already presented, it is obvious that personal bias enters into this type of an evaluation. The widely varying opinions given by trained scientists at the DDT hearings conducted by the U.S. Environ mental Protection Agency emphasize litis point. Opinions on the impact of DDT ranged from the viewpoint that to ban DDT was gcnoddnl to that DDT was a universal biocide. Personally, I he author dislikes the idea of any stable foreign material being released into the environment on a large scale, since ecosystem Interactions are too complex for any experimentation to make certain that no serious consequences will occur. No definite evidence k available to indicate that current PCB levels are normally a hazard to human health. In view of reproductive failure of a mammal (mink) fed fish from Ihc Great Lakes, one would be doubtful about the safely of persons on a high fish diet in the most heavily con taminated areas, viz., the North American Great ijtkes and Japan. No evidence is available that PCB's are carcinogenic or tclragenic to mammals although one could wish that I he evidence was based on larger, loiigcwange experiment*. The reproductive failure of mink fed fish from lltc Great Lakes under laboratory conditions suggests the possibility of effects at current environmental levels on fislt-caling mammals. No field studies have been carried out with the exception of sea lions In California. In this case, however, Ihc predominant residue Is DDE rather than PCB's. The reproductive falluie of Herring Gulls in the Great Lakes is piobably due, in part, to PCB's, although the relative importance of PCB's compared to other contaminantsis dim cull lo assess. Similarly PCB's arc probably involved In the declines of other lop predators, i.e,, Osprey, in eastern North America. Laboratory studies indicate the toxicologial effects would be expected at higher environmental levels. The importance of PCB's and other organochlorinci in selective advantage to microorganisms in the environment it difficult to assets. The possibility of alterations at environmental levels is suggested, but actual confirmation is not available and would be difficult to demonstrate. The author's assessment of the environmental impact of PCB's is that some advene effecis have been caused lo organisms high in the food chain in highly contaminated arms, such as sections of eastern North America and Japan. One lesson to be learned from the PCB story k that a stable, lipophilic compound can accumulate in significant amounts even when not deliberately introduced into the environment. The information obtained on Ihc relationship between usage patterns and environmental levels, and ihc alterations following restrictions on usage, should serve as i basis for future rcgulition*. 1 Hit 1 1.r 1 \is J V t Mj h Vi j rm i 7 M1 K Sil' a i in jin in Sf,. ,N4 it U.J \ 1- t.` Mm. ttirf it tiro tl.it ta 11i-1 IV Hal 'f tr. U 1m 17 IH ' IH Ho / 'i ie II a. in fj f K. * 'i Sin ^ j Hut ii Kiv. _4-N1 Krv Jnt .'h 27 lljt t SI 2`> nil in tUi n f .it. it- i> n b> 34 t-i HONS 206876 r: AL liable lhal n,animals ilencc was s I fish from conditions <i current iimali. No wiih ihe i this cate, 'PE rather if Herring <ic, in pari. <r lance of is difficult involved in Osprey, in ly studies tic expected tier organoixii|inisms isses*. The rial levels Is ml available vnonmental ffecis have v*d chain in sections of >ic lesson to ,i I a stable, it significanl introduced w obtained i.ilierns and his following a basis for KMIRINMS ` 1 llulrinect. t).. Safe, S., end /ilkii. V.. /in- r /iiimoic / IX 'll V. I IU' t'u-s-.. r'lvicl uni Dlnn. 1474. 2 Pruning, C. It., Physical cliniai IviisIrv ,im] i-num.iii.il pussd'ilnics til clilnimated ihpluMivt. Itnl hix limn , 22. IIKII. Id'O ] Nisliel, I. V. 1. anti Sendim, A. (Kales mil mum <>l Uampnil nl Ifll'sui ibv vnvu-nmi'iil. I in tmii IHtil'Ii IVn/wr. I. Jt. 1972 S I'aiiagrurge, W. H.. |hms<i:iI s<iintirn> alum I'lTS 5. Maugh, T. II.. IIHI: ail iinreynpuiri'ti mnmc ><i i-,l>ilii-ii-i,ic,l 6>|,| ck. v, i. .v. ikii. C7H. 197 V r, Peakall, |7. (1. and I.Inver. J. I ., I'-ilyililmm., Ini bipAivnyk humlIki Innc-ldc SHtviiiii-jtl clieiiticjl hi Ok s'nvtHHiiniiit. Whi.S'mViii c. Jtl. VS*. 1472 7. SCI I*. Stud) nl Klli.il viivininupcnlat pii4lciPis. t/iiii i /iH/nr I mi fhr r.'Aihjl /.KijriNiiiitvii. Nil I'lin, I'ai-hi l):i. Mass . 1970 K SHii, D. R. and I'oiiotan, I . I ., Siitfarr slicks hi niniTitluiiin id |HM.lhhIis in IIh' maiiiH' miHiwmi nl. /', m, Minn I J . 1. l`Ht. I dr.') S llarlung. K. and Ktingkt, (I. w., (niHiiitialinii nl Dili by wliHK'iiii'it pnduline dts.l.orWmt ,Vrt iivini.il. 4. 407. I4TI1 10. SmmHska, N., Iltmlcniuii'tl i-jiipmmdi in tciwili'i vliiiiiiialniiiapliisalty nnilu hi R'S'clki tnllnt Hull. .'. N4.1474 11. Hulk-man, T. I\ and Cllncy, C, I ., (lilniiiuliil liyil/nmitium m |hc Sjiifiwi .VJ rinmapitcii' mid miiIki' an t. Srlnttc. IH.l. Sir.. 1474 |2. Morris, H. I., I l|wl ciMiipnsrliiin id tuilnr libin ami /inipliinkhin horn thr I nli-in Mi'ililvn.IIH'H/I. i/ai l\tHnr Hull. J. Id.'. 1474 II. Horn. W., Kinrtirmigh, K. W, Snutlr, A., and Vming, I). R., Hepmiin*ii nf |l|H ami pidychkiimak'd hiplremls m UjU'il hiIiiiiiiiK uf I In1 Santa hnl>iti Plasin. Ai lirnr. 1K4, 1147. 1474 14. Holden, A. V., Source nl fmiychlnrfnak'tl biphenyl miilaiiiinalrnii In Ihc matinc rnniiomnenl. Aalno . 22S. I2JH, 1470 IS Hakim*. W.. Mictuy. <l. w,, and Hogan, l,, 1*t'H Icrrli in Clyde maimc sednnenis and lamia. Htr I'otlm Hull J, 154. 1474 IS Linko, K. K., Ranlamaki, I*., and Lljpo, K,, It'll icudues in plank inn and mlum'in In the iniiiliwoh'in imu i I inland. Hull I imii Ciim r.sufW.. i2. t*m. 17. ()pstfi4 R, W. ttul fivhtii 5m ('hlitriiulnl liydri;ailHft* in IHH.197* hiOkvi> litmc. Mur /Wiif Nutt. 4. |H RrwnuCa A. Ogata, J. N., and Ityl'n. J. Oi^nmliloriiic |^1kiiIi,> in famwaU'f, Oatiu. 1971 "Il, Null t ttwnm. (iMrifftir `I'mVffW.. K, 27H, 1972. |9. Harvey, (. R., Roweri, V. 1Itnittiy K> II., *nU ( trice. Cl. 17., I lll"rHi-ilul III itincitrlionr in Iipm-incan All.nlJl, i>ie.inknit. in /' UnbrlSriUH . Iti.tlicnlmrp. 1471 20 Carts. D. I:. and Ixwis, I). t-. CIhiiikjI and tnicnilMal dinrarluiHHi id n il nk-i ini cimiivuIim in m,h:iih h iI,mih. firvidnc Hit.. 4V4t. 1977 21. Knrdergian. A., Chltinnalrd liydini'ailiiin icsiiliieii in aolHirih' tallnoi. ^rriiii , 2.lri, .Ids, 1472 22 IlnHeman. T. I-'., iiciuhuI riiiiiiiiiiiinalHKi, I47S. 25 KiscdHiwgh, R. W,, Krichc, I*., rrlkill. II. R,, Hetman. S. (;., and Kimrn, M. N., Pidiililufiiulc.l hlptimi I. in tin- HuImI ei iKyoeni. Ntmrr. 221'. III9K, IdfiK 24 l ikiii, T. A. and llo, J, 7.. Invesligaliiin ill llic aliiiini'liinli |H>ihnnin itli Ik li in a mi, f iinnm I'.illui Ki t. 2. 25. 1975 25. KinetiriMgh, R. w,, Chhinnalcil IlydliMallmm, in lm/HOX< inillt nl Mu" mi dir riivaiM. IIikhJ. |> \\ . I J Itilciscicnce, New Vmk. 1471, 2S9. 26 (Irene, P. A,, Ptilenlially ha/aldnus substances in mirtacr *ilri>.A'rt Tumi I nunm., I. 175, 1972. 27. Simpson. R, C. J., personal cnniniunicalion, I97S. , 2It. Ilarvcy. (j. R,, Slrinbauer, W. G., and Teal. J. M., riilyehhirnbifiltcltyk in Nnrlli Altanik Ocean H'II.M. K iirr 1 HU. 645. (975 24. Otnry.C. I.. and 0*inn. J, J., unpublished rrsulls. 1975. It'iieil in Releremv 5n.i 50. Harvey, (>. R., Mlklas, H. f,, Howen, V. T,, and Strinhaucr, W, (['.. tHncuatinns on llic dislributniii nl ddnritialrd byilrinalbnna in AlbniH- (Ktan nieaniviis. J Afar Hrt. 52.105. 1974 51. rirKe, (. f)., Harvey, (i. R., buses. V, T., and Haciuis, K. II, Hie cidlcvtimi ain< ihckiiiiihs id n|icn mean uialim- iweannnls fin pntlul.mi analysis, ftirfr, Sniwm (imiain 7ii,iim/. 7.125, 1972 52. Scrwen. S,, Rrnheig, I.., and Olsann, M,, It'll inn IAmman,hi Inun Imai Ihniuni jiaml amt link ul It'll m |i1aokt,in nutodc a pnlluletl area, Nttutr. 2411. 5.5H, 4472 55 Harvey, G. R. and led, J. M., It'D and Hydincailmn cnntainOuliun ul plank Inn by m'ls. Itutl huinm initiam Jiitrnd.. 4. 2K7. 1475 54 Were. I). M. and Addison, R, l-',, PCH rcsidm-s hi plank Inn limn the (iulf nl Si l.asim, Nxiurr, 246. 514. 1475 Sc|*k`iTN'f 197% 501 r #> MONS 206879 IS Jrntcii, S., JnPneU, A. (Maaon, M,, and llllerlind, Si., Ill'! ami PCM in mailin' imnn.ils limn Sue,Ini, tulei*. Ntlurr. 224, 24r 1969. JC Jcmrn, t.i Jfdinela, A. <>., (Muon. M., and (lurrlind, t;., MU I mid PCH in lienin*- ami eml *rnni llw Halin', Htf kjllcyai and Hie Skaecir.ik, .liriPm .V/nr. /dji . N 1.71. I`>7J. }7 Wnfrtci (i and Nmen, K., K1i*|h'*Iii'hI'<h.Ii pniykimliilt'iivlhalitn i livk l.iiikad i aveuika vallrn I'lk'i mini,ml i SveMpe 1967 1970, Vi<- / </#. 22. V.l. t97n Jj Keinke, J,, Uthc, J. (..and Jatnicatm, I)., iliAanuelitmiiH' pmnii'>!. n-tnUiet in emu nn'ii Mill ranplii ndt ni Canada - 1970, /Vwr U<miwr J , h, 47, 1972 19 llrndciaun, C-, In^it, A,, and Juhnaim, W. L-, (HfjnuMnriiii' mwi l it ide in Pali tail I7M, IVihi Mntmor. /, J. t, 1971. 40. Cm, K. L., l iniltwiklci, C. 1., and St-hihi, M. J,, Cl.emu j) untilnetm I ake I ite li'li I97H 7|. trine Mtuuhir. J. 6,23. 1972 41. /.ilko, V. and ttutringcr, Cl., Cmiiaiiiiiiaiinii nf Canadian All.min injiliil aieav niMi |n4i ehlm itu I ill hif'lient I, IPCIII, pnlyeldniinaiiil lei phenyl* (PCI) ami uljietl TM,i|,,wwk. .VWnif(> iti 1 nr kktm H<t,l,H I ulthtj lltrhn-DtiMrm, 37, 121, 1972 . 42. Zilkti, V., 't rind I of PCII and OUT w lieh ami anuaiti hiiih, in liili'iiialHHial 1`iintiTfmr tm luinpml td Pciaistcnl Clienneali in Aquaiie 1 etyalenii. l'im Nail Kn t unmil. (Illawa. 1974. Ill 4}. Addiann, It, I'., Zinck, M. Ik, and Aekman, K. C., Htmlun myiHiiulihiime peMhidet and pol>cMnfmaifd biphenyl in antin' eiiromcriially pindiii'i'd Canailun maim, nils, J l td) firs. IhmmK'mt., 29. .149. 1972 44. Ciani, C. ,, llanka, A. It,, Kiehatduin. K. I... Saitrll. M,, and Kong, HI. K,, DH I , Dill and ptilyitilmmated btpiii'nyh in bmiii Iiihii Ihc(ialf id Mi'iii'nihkI ('aiiMkin Si't 1971. f'ruu AJiiun, u J. I,, 1,19, 1972 45. Cham, C, ., Rtchirdaim, K. I.,, Taylm, II., and Wnng, M, k.. Hill, Dill, and fl'll'i in Ilk- Iimwi nil dwelling pumpers ISeirjmdic) in the Gulf nl Mcvieu and the Giamt ll,|liatiiaa. Hull /inirmi (mum,) Textml 11. IK9. 1974. 46. Ddfucbi. M,, t'hhifinalia! Iiydincarbmu iu the envimnimnl in I lie kanin Ham ami inkyi, May, at lelltiied in ftdtca, bird* and man,.Voi' Mrllttnlt T.m irtm (ln.li /ViiioJ . 269, 1977 47. Fajia na, K., ! Jivinmiiienial and Imnl omlamin.ilimi willi isn't in Japan, in Jii7w. OrjHntrflettl nl llrfirnir Chrmlitrv, kynlnCily InmHilr, Kyitlti, Japan. 1974 48. Solly, S. R. H, and llartiann, D. L,, DDT in amne New Zealand ntjtine am| lietlmalci fauna. N t. 1 Alar 1`mlltttlrr Jfrt., 6. 4A6. 1972. 49. Neuhatt, J. TV, Riady, M. N., Kiyali, I), S,, and Wallia, |.,, Mt uuiv ami meauin lilminv peMn ulis iu lith. Uni J Aud., I, 1117, 1971 50. Ciillicrtaon, Pnltuiaiilt in hueiliitR llerfinu CnilK in ihe l,,rr tueal l.aint. (tin J k Ii! .\`tn . nn. 271, 1974. SI uicik, J. I;,, and Hull, C,,. Rcakluea ol 1)1)1 and I'Cli iu rn:< limn Ih*iime *mI 1/unit uiivnijiuil and imnniun pill (iann wiuiI in N<*iv, diK IVi. ,7'itnil. 12.429. 1971 . S2. Rl*a. U J., Nealy, fe, S., Ji.. BtHide, A. A,, and Piouly. R. M,, UiyaiHit-ldmiiie n tnlnet ui llimtn Peliejn ej4it lelaiinn In icpluduelive nieteaa, tmin/n. Pnhul., 7, B I, 19 74 51. Gdlterlann, M. and Reyntdda, l., IHH amt PCI! in Canadian liinh 1969 1972. (an. H'lklt. ,Viti., IInti. I'ti><rs. Nn. 19.1974. 54. Ttcple. S., unpubllthed iraillia, DJ6S 55. riacbroitgli H. W. Mil de Lappa R., anumuiaiitan n/ /u>iirhluritiatrj M/dimth tn ,- <i tn-mt. I nvin.n lleapli Peiafteel., I, 39. J972 56. Rydei, J., OryamichUitinc and nicriuiy levulnci in |ilh` ryp iiihii amein ilnimni. Cun l irhl Xtt Kit. 749. 1974. 57. Hunt, G. L.. Jr., Ilunl, M. W.. Rhebrmiglt, R. W.. and (irett, l;,, I nliikv lata Pnnimal painna ammia Hftlcra Oulh nf hhiIIktii Calilninb, unpuldivlied manuuiipi, I97S. 51. Rlut, L. J Beliak', A. A,, and Tiuuly. R, M,, HtiblHwirl Uh; Mmmi In trilitin pulluMnh. FrxUc. /, 7, |H|, 1974. 59. Jobation* D. W* Ptilyi'liliwinunt biHwJnyU In ua hlnK Imhii AwvinMm Kbml. Siniiti Ailjtuk Urtun. Htt kmlrtm. Tn.ximt.. IU, !WH, |97^. 60- Tempi**.1!, s4 frtkti, I). UM wnpubliUirtl icsiilu, 197,5, 61. He W, ltd Cl OiliwiiiaiicM hyilMH.iflHms. it\ AiiI,miIii I'imK in / ihr i tdhHtuium, CuHUTtvtiMt tn Antn ti<ih U I tl , Alk-ti |la*n 1972. 62 Ja U md l iw, 17a K 11. in tlu.k Aobruii , 7 . l/r/t/ t int. } I. 1^, Wtiti 6). TiHra(J.II, (i. ltd KmHHij, J, |l. A,,Oi^iMiHMnrim |n*Mh Nk'\ m Annn Mi ii..VfiHK . 215, *4(1, l'H7 64 Bf*cttrupk fM, ClMira, ami herg* U.t hl>l., |Vf| dml aUlfMt kvt h in Ait lie luiilt ,ii I.,I i tiljml. Hull J ii.'iimi (VnMUL 7(Mirn11, 326. 1974. 65. Butifiie. W, R, P, and Hogan, J, A,, Pidyililnfinitud Piplnnyh in Nmili Ailaiilic aeakinp. Afar. > nlltti Hull., .7. 171,1972 66. Brnniti|lnn, S. L., Connora, P. C,, Ctmnota, C. TV., md Kiachiuugh. R. W., I'aliemt m thlniiiialtd litdim jihtin emMaminaimn in New Zralaml ault-anlaiiit and euaalul niunne Piidt. iiii umi tulhtl . B. I >S. 197S 67. Dante, J. C,, Rcaiilujl mpjmHliInline pcalnidef in ihe fai ni iiiuium PrnK | New Zraland, Hull Jinmnr Coniam Tuitcul., H.S17. (974 502 fftt CritutlH n frni ti* tiivirtoiuirinoi < utttr^f HONS 206880 6k rird. filial 69 1 h*\ lli. i- 7U { ilia i ill M H 71 lltdd Ml 7, 72. A JiO l iu i 7.7 1 fn l t 4|`l 74 H.`1M 9'llvil 7S 51811'. h-.t* 76. Tcin /' fr. 77 iiir, 7k h.oli. |Q71 79 Adds BO lin:i n*Mu Bt. SltJU *2. IM . Iiihii 8.1. SlM l M`-t K4 (ijvt Mire Hs SC I'CBlv Kh K*hi M7 Kim r-hk la K8 Wien Kim. sIvM N9 Bril's Odii fur t- 90 Prjt 91 Uill i lull 92 Pelk 93 1 ftdi 197-' 94. R*tk u7. riL 9k ImA pal 1 97 Kura M). ' 98 C*nl / irAji 99 Oku 60, ;dlsh * .Hi I'. K' llulltl HO er ulukird i lupin lull m 1969. Pi tor In Monitor til litplinlvli drrr / u/rhi'p liampuii nf lyclilurinalcd 77> lycldrunijicd 972 eel dnvllinp ml. II. Md) t rclki lcd in 1 til Ih flr'iH N 7. J Mir i in (tth. AfrJ 73. (974 and riimiuiin Ptlnan cyy* Urcfl 1`tprn. rtlnn. Health War.. NO 349. towny tkceiern nial pwHulanm. c Oican. Dull rtlllllfl t>t thr rru, 1972 1967 . Hull I nrtnnl rotlu) Hull 3. ,-d hidnuarbun IS Hull llttirtHt 6B. 69. 70. 71. 71 73 74. 7$ 76. . 77. 7*. 79. 10. 1. (1. (3. 14 - *5. (6. 7 IS. (9. 90 91. 91. 93. 94 9$ 96. 97. 91. 99 fltdiiw, I. I- I'. Mi) Jrrfrmn. IV )-. Kelali"ndiip IkIwitIi iiip-iiimliloi mu tcndhri. in h*en and ttlmlc bndiC' i.( ptilli'Hi'iii. /jiiVrfMi I'ntUii , I. H7. 197J Uitfd, t'., Hogan, J, A,, Hi mini'. W, R. P,, l)iwn, I*., rartlnw, 1.1.. I,, iml Slrnl, A, <1., Soilnnl mtuiulny in llw mntli I ritj> .So uivl (ir111 * 'I l !yU otlv in 1974, Aim. < Hull. I, I V(.. 1974. IJoiti, J. L ni) Prakall, I), II., II 11 |ili3nii,M Nly.niiiii (| Htr KHip |lmr anil curly c]ii'liinmi<,iyi)|>lih I'lA iliiiiiiHilinn, Knriron I'ltlltil .t, I'l. I'l7.1 I1<Men, A. V, M iinil in mp ill pirnKlill>r ini' 11 in i.1111 u I111, 'll nl Km m.n I In I'ln i milmi'll I In * III anal) ill 'll I i'll,) U,, In vuli, in jUanm* /W/i/iiiHi and .Via I.it,1. Iieliiny Niii'* IlliaiUI l.lil.. 1 niiiluii. 1*171, 26b Addiion. H. I ,, Km, S. R,, anil Dale, l,, Vaiialimi ul wpamliliiiiiir midur liirli mill ape in (lull nf Si Lawrence harp roll I Api/ilii/in Eiiicn/iiiii/itnil, / / fi/i An. IHuti.l ( till , VII. IS,', 197V. Prank, R,, Ronald. K., ami llrian, ll, li., l)r(.innWiitlnr nikliii'i in l(a>|> Seal* ir<ip||iliil|ii friurWirii'l rmiilil in imiIl'iii I a nailmu ualcii, J l-idt. Act Amn/Caii. 111. IOVt. 1973 Ikiwo, G. W. Mil Innkrl, C. J.. I"iciiht arid ilivliiliuliirn nf |H4yrhlnrinalctl IliphenyU (PCtlt in anil, mil ti'liiirciH murine limit i liaiin., J Itdi Ar t. Hoard Can.. in prem. 197$ tlauacn, i,, tlracrtrwp. L., and Rci|. O., Ihr ruiili'iu nf |H4yiiilniiiuliil 1i|ilnk aihiMi* in attire niainui.iK. Hull Httriron. (Warn Toxicol. 12. $29. 1974. (`caret, P, A., Glnrhy, I. M,, and Keith, I. A., link' iIk'iiihuIi tit Unity ildnp In the Gulf nf Rt. luainai. in i|u Tettindr Scrfimi (W Wihll X<rr Mamttrr Hrp, Nn 24, I97.V I leppicttnn, P, H,, Oryannchlnriiica in llrlltsli pray train, Mar I'oihit Alt//.. 4,44, 1.97V. Catkin. D. K., Prank, K,, IhddrtMt, H,, Ithida, K. Wallrm, C. J. and Knailh. M, Mrrctrrv. (till, ami lt d in harlrutu Kill triplet riluhnal from the Hay nf I timty and Gulf nf Maine. J. huh. Art Wncrj ('mi. Vi>. 47i. 1973. Ana, R. I., I a 171 pint FOI't in blubber nl h.trlim trait, i'rtin. Uimlim. J., It. 12, 1974. Kncman, J. II., Pertet, W. II, M,, Smll, C, J,, Ipnc. P. S,, and DeGorij, J, J. M,, Pcrtblvul chcuikah in mannv manimalt, TNONiruwi. 17. $71). 1971. Shaw, S. I., Chlorinated hydrocarbon petliciikt in {'aHTurnia tea ttllert and harbor aealt. Calif hilt Oaop. $ 7. 190. I97| DeLong. R. L.. (iRmnllt, W, Ci,, and Simpaon, J. C,, Premature hiilht in California tea limit: attmialmn n illi hiyh otyanuchiurinc pollutant rcthluc leech. Vrlrarr. (HI, i IAN. 197V. Saacbcnhrccker, P. W,, LmVi of DOT and K'll compound! in Nurtli Atlantic fui-bark whak*. Can J Coinp Med.. 31.103. 1973. Catkin, D, li., Smith, G. J. D.. Arnold, P. W., Iamity, M. V., Prank, P... Ilnldrinct, M,, and MeU'ade. J. VV,, Mercury. DDT. dicidtin. and PCB m twit tpveiet of Odnuluccti (Crtacral (mm Si. Liiriu. I.met Anliltci. J lith Rri. A'*crJ Cim.. 31. 113$. 1974. ,, .rcakril, IT. 1 Dill : ilt ptvwnrt In |>CrcyiiiM.'epyt in 194It, Seienrr, IH1 1-71. 1974 KoetnM, J, II., Iladdcrin|h, R. It,, and Bijlrvrtd, M. C. I, J,, Pertitirnl polio luiin in the whiir-iaikd riipk m the I cdcral Republic nf tiermany. Arid CurttrTr , 4, 373, 1971. Koimtairi, J., Laaniaacn, A,, Nnuja, l,, Pahrkangat, K,, and Vlbktt, V,, Nolen nn Ibr cimcenlTalinm nt mum' cnrironmcnlal chcmkalt in I be cyp* (lie while-tailed cayle and Ibo m|iiry in (lie Uuarkvn area nf (lie 1 .ill I nf llnlhnia, Work tniirrwi. HetUh. 9,44, 1971. Wemcycf, S- N., Muiheen, >. M,,, LJfii, l:. J,,llrnarl, R, J., Mathnen. J, l',, Rohardt, f. C., and Pualnpaltky, S,, Retidues nf iirganiH'ltlnrinc periicide*. pnlycldurinaled biphenyK and mrreuty in ItahJ capk cypr and I'tiaupi" in ahcll Ihkkneu 1969 and 1970, Pc/tre Monitor J . 6, $0. 1971 Beliflc. A. A,, Reichd, W. U, Locke, L. N,, Lamonl, T, G,, Mnlhern, H, M,, Prouty, R, M,, DcVVnlf, R, B., and Cromarlic, li,, Rniduea nf nrpannchtoriiw pcttrckln, pidyrlihuinaled lri|>hrnylt, ami mercury and aulnpty data fur bald ca0ct, 1969 and 1970, Petite Monitor J , 6, 1.1.1. 1971. Pcakall, D. R,, Cade. T, J,, Whih, C. M,, and llau|h, I. R,, Orpanuehlnrinr rctlduet in Alatkan pereprme, Pt tlir Monitor. J.. in prett, I9TS. Walker, W., Matirvx, W, r,,,and Riarbrough, R, W,, Pollutant and ahcll thickm-tt delcrminaliont nr percyrine egyt from Weti Greenland, Arctic. 16,2SS, 1973. Ptakali, D. B., unpuhlithod rewillt. 197$. Sndeiaon, J, II, and Craig. 1974. Stalin of the peregrine falcon in the Rocky Mounlaint In 1973, Auk. 91. 717. Ratdiffe. D. A., The percyiinc population id Great Miilain in 1971, Bird Study. 19, 117. 1972 PtakiB, D, I. and KMT, U unpiihlnhed reunite. 197$. Ttuk amoto, 11^ el it., Chemical tlwlici mi deter mm nf link cnnip<>uiidt in I)h- ter hran nili uwl hy <lic patientt of Yuihn, I'vkrtakt Artt Med., 60.496, 1969. KurtUuoe, el d,, An eptdemioloylc aludy im "'Yiuhn" nr etih;;,rhiphrnytt p.ihnningi, I nkonka li Ah J 60. $13. 1969. Gnln, M.. and IligueM, K,, The lyniplunialtilnyy nf Yudin (rhlnritbiplicnyli pniMmillyt in di-nnali>hi);i, I'iikitoka Artt Mril .6(1, 7, I9h9. Okumura, M., and Kalmki, S..Clmicai nlxa-rralHint mi Yuthn Ii'hliiri4ii|<hriiyli pniMniinyl, iidunir U ta AInl 60, 3N, IVL9 Scplcndm 197$ S0V ' * >t . Cw :(i * \1 A* f'-2 wins 206SS1 100. 1 (II 10IA. 101 it. 10IC. 1010. 101L. 1011`. 102. I0J. 104. 105. 10*. 107. 101. 109. 110. 111. M2. 111. 114. 115. 116 117. IK. 119. 120. 121. 122. 121 124 125. Kohanawa, M., Shoya, S., Ognta, Y.. Munwali, M,, ami Kawasaki, M.. I'oiMmmj: (lire |u an oily hypimluii nf ricc-brao timMai 1" chick gdmia iliKau1, I. Onum'iut and toxicity Ki, Ntl Inn A unit llcwtih (). 9. !l >. 1969. . Brwlry, K, l,,, lr, NliMmiulnl biphenyl* in wan'* lil inm'i i AhH t u.il t*An.d., lt>. 155. 197 V Ililfnian. II. T., Nnieie, ctfahtunyui mil lim him nclicM i idrklit<'Un>a*M. iiimlm. . ifi ti I vj. Pllh-A Pturrml'A 112.22*. HSU. Dun, II., Sdiult, K. Il,, (ml Spir|riliti|, V., Herullnltr Vi ipitinnjini bet tin Iniuclluny nui vcrbrndunjcen, Art-lt. fiVuv/ir/ieffnd (irwithrhrg., IH, 51*. 1961 Schwclr, 9. A.. Nmiii, I. M,, Sparklicr. (i. L.. Rowe, V. K., i.chr!n(. P. J,, I mni, |. l,,, mj Sribif. (*. (I.. Toiicnlticy iif ihtiiiinlcO ini, fiiwoM //.a!lit l , V H7, 1971 liui, V.. Hutr.in|cr, O., end Ora, f, M. K,, Oiilaiilmalioii *1 iltr Hay nf I umly-l.idl >! Mam,- i widi pnlrcliliKiiulcil biphenyl*. polychlorinated tcr|dicnyl. ililnrliuiwl dribwiilimint ami ililicu/itlutan* A'hiwiui llrgllh Pmprtt.. 1,47. 1971. Bowel, (i. W,, Simuncit, I, It.. Burlingame, A. L,, dc Lmppr. 1). W,, and Riwhrmifh, R, W,, T he (catcli fix chlonnalcd diltcnrofurau* iihI chlorinated dtiH'il/jxIhixMl, in wHdhir p|>la<i<ii tlmwiny HotilpJ Mi of embryonic death. Htninm. Health I'rrym I , S, 191, I97J ' Nonlrom, K,, pcnonal tmnminiicalmn, 1975. Kolbyc, A.C., Mo threat From PCH't. CTum. Hug Newt, 49, II, 197|, Anon.. Ilnlutr wane h**h\ {Urm hVtd, 1117, JI. 1972. Price, N, 0,, Young, R, W,, end IMckininn, J, K,, I'cxlh-idc itoIik i ami pidvchlminaliil hipltrnyl kveh in deli. Mine imI Inal miiiu nl piQilnIcucnl prli. tW Air Hint AteJ . 119.111111.1971. Burro, J, E,, Organochhirinc pcilirilt ami polychlorinated biphenyl inilw'i in hinptird human adip.wc ikiut. Teat* 1969-72, fr(ffc. Mtmliur i . 7, 111. 1974 Dyment, P. G,, lleberlton, L. M,, fiomct, E. l>,, Wincman, J. S,, and lliwnibrook, l|, W., Absence of pnlycMmi naled biphenyl* in human mttk and Mruiu from Ti'in and human milk from New Guinea. Butt, tannin f irritant. Tuxieot. fc. 5J2, 1971. Siyali, If. S., Pniycliloiinaied hiplicnyK, licaaehlurohcnxcnc and other oryanochhirine pctlieidc* in human milk. Mni J AuV . 2. HIS, I97J. Finklea, J., Prieeier, L, li., f'reaann, J. P.( Hauler. T., Iliwn, T,, and Hammer. I), I., I'oiyrhiorinaicd biplienyl ictiduc* in human plonu export' a majiit whan pollution prohicin, lor J IStMte 'Health. 62, MS, 1972. Ahe. J.. Innuc, Y,, Takamalia, M,, On ihv retidual armmnls of FTII and ntaaimclilmini' petlkidn in liiinun Mmid, Niftpuu t ltrrftl i; /rntli. 19,91, 1974. Inuuc, V., Abe, 6., lathi, ))., and Takamam, M., Pnlychkirinao.il hifiliciiyU mi liinnaii hhuid, Airrumr' Aim/ J . 20, *J. 1971. .Jnrwc. V., Abe, J., Takamaltu, M,, and Aoki, N., A slwly <m Ilh* iiiuliijiivc and i|uanliia1ivr ijMo or IIH ami orpannclilnrim: pcathidi' midnrr in the hlood ami Hie ;hIi|hhk iumh. A'Uiftun t Morjcoirr 29, 9J, 1974. llrawtherg. R. J. and jkken, Ik 1)^ PTH'i ami p.p'-DDI in Mie liUni of talK'nic paiienu, Bull t.ixinni (rinMln. Toxkut, II. 102, 1974. thiota. K., Tanimura, T,, NHdiimura, II., Miwlani, T,, and MalHtnidlo, M,, Pnlyvhhirinaled hiphenyla, 1(1 If and Oliliin human fetal buuct,Stttirt t(o. 1.1, 179. 1974. Markin, C>. P., Ilawlhmne, J. C,, Collink, II. L., and l-urd, J, M,, level* of klrrex ami inmc other ivpamit'hlutine reaiduc* in KaftHid from Allaniie and ttulf cnadal rule*. Pvuir AhmiUw /. 7, 1.19, 1974 Fotd, J, 1I-, Hawthorne, J. C., and Markin, Cl. Keuduei of Mire* and certain other ehlorinaied hyitiocarlmn mneciieidct In beef fai, 1971, /\*tic. Monitor. J., 7. *7, 1971 Vllleneuvc, D. C., KcyMdda. I.. M., and PkBUpi. W.C. J., Ketklnc* of PC'H'tand IVTi m Canadian and impuiled Vuropcan chevtci, Canada 1971. Prate MtmiUtr J . 7, 9S, 1971. Met, J,, Coffin. D. F,, and Campbell, D., Polychlorinated biphenyl and otpanoriilorinr pctlkide tcntluea in Canadian chicken eppt. Prate Afoniior J., 6,1, 1974. Ijed. I. E,, Rnidaci of oraanochlorine mKc'licide* in (ample* of Norwegian butler 1970, Noxi Yet Mni, 21. 906, 1971. Savapr, K. p.. Temarl, J. O, MaHrctf, J, W., Wheeler, II. W., and fiaBhy< ^ Hn Otpaiiaihhkwine peilickle residue* and polychlorinated hiplicnyl* m human milk. Culnradu 1971 72, Petite. AUutiWr J,, 7, I, 197,1. Mwdal( C, J., Hutringer, 0, Zitku. and Cmckrt, J,, Pfrteme of 1TH. 1)1)1. and 1H>I in hnutau mBk in the province* of New Hruntwkt and Nmra Scotia, Canada, llult. AliWnro t on mm 7<ni<>d. I2.2SK. 1*74 Birth, J. F_, 1M)T and PCII rcttdne* in human maieiial from Norway. Tkhtkr. Ntutke t.trtrUuen 92, IS, 1972 WcNOOiG.and Noren, (fir. finfe, 24,4|, 1972. (Cited in Helereihe 121).I Acker, L and Scbullc. E, (Keurrrnrc of dtloiiiuleil biphenyl* am' hr\a, him otwnrene lop tlrer wilh chlorinated inttctklc* In human milk and adtpoac ttmnc, A'etirr nim* he.' i n. 57. 497, I97IV Wetlon, Chanyci in the IcveU of cnvtrnnmcnlal polluiant* Illy, HHV. ilichlrin. ti lt) tn tome Swedmh fond'. Amhitt, J. 79. 1974 Price, II. A. and Welch, R. L., Occurrence of polychlorinated hi|d>enyl in human*, ICiirlroii. Iletllh Prryperf, I. 71. 1972 IBt CMC CrMttt Hrrirw* fit f.ttvtr,mmrIItut (imrrri MOMS 206882 126 121 17* 129 v rAdi 1.1(1 111 H2 1 VI t .14 I1J 1 >(S 117 1 IS 119 140 14) 142 14.1 1 !> k r '"V> Hi 7.1 i*. P .. itM'l' (If. 1 r< lw. K-l K'f h*r' Ci.n 17 il* : Si(Mf rv 1 144 VVdf, 145 1 46 147 14* 149 150 IS 1 152 15.1 154 I5J 156 157 |.IK 1 J. IIji it i M*k d.<i IKA \kih 11*1 HI'.' \|k*r -l,r/ Bvm f\|' Niki *l*ii Kirn p. iHiifP. .Ik d>k i Aii> p..li llfif / 1 ill no, 2,"> loducl of . 9, 113, J5. 1*73 tothol nrpltniol' if(. C. rc> wiili > t'maroii catch for I levels of ds Indicts. wtt tiller, ibicnce of met. Ml intM milk, tl biphenyl 'J. i ip human nr Med. J., of mi ant) . 1*74 ' tnrlroh.. 1. MIC and MCtlturine *dtocart>o M) Itnpotted rcnduei to i Med., 2), Ntc tCHdUCI < talk in the >4. 2. tJ, 1*72. nether wilh cdiih foods, Penptei. I. 126. 127. 121. 12*. 120. 1)1. 1)2. 1)). 1)4 1)5. 126 137. 131. 139. 140. I4t. 142. 143. 144. _ 145. 146. 147. 141. 149. 150. 1 Si. 151 153. 154. 155. 156. 157. 154. Voha, A. R., I.evels of polychlorinated biphenyls in aili|>ntc tissue of llu- |cmi.il |HipuljtHin. Cnvimii llcallh PmpeCI.. 1,7*. 1*72. Alter, 1-. and Schullc, 1:.., ('libitkiihlciiwjmorsioiV mi niiiisvliliclicli 1 t-li A'aiiim-iti, ,i,,h,Hi,,i fcl. .13. 1*74 FmAirfn, It,, Klehlet. 1., and irlnfVe, I-.. tiVrr A/r rc... hi IS, 31K. 1*71. iCned in K.-u-.oi.t .'it i Waucrmann, M.. Accumulation of piilychli'inhydio.:<ilnm in humans hi In o h Aip/nn A'iuoii leal let /atdtt, 22. 772. 1*74 tiro*. F. J., Walker. A. ( ., and Medhety, A- t'nlyeliliirin.ited biphenyls in hiiittait adipose Iumii'. Bull Tntium CrUIMm. Tornot. 5. 317, 1*711 Iloguchi, M., Kukani., 5., and Uubhi. I .. I',.lyi|ii,itin.ii,,l ter|ihcnih in the human t.ri, Bull l nnmti fomam Irurntf. II. 157. 1*74 (>tanl. U. L, and Phillips. W. I:., 7 tie cflecl nf m and 't on (lie toxicity,nr Amelin 1254, a polvilikiiiu.ind bipliunyl. In llie ti, AnW Innraa Co main. 7ovi.nl 12. 145. 1*74 Bruckner, J. V., Khenna, K. U, and furnish, II. II., Iliolnpical icxponw* nf die tal In polychlorinated biphenyl*. Turin*! A/ifil litantiaiul. 24.4 34, 1*7 3. Tanaka, K. ., I'ujila. 5., Komatsu, I and 7anrwra. N., I \ I*miinMai aihKnlr poixoninp nf JbliitohiptnnyIV parlicuhirly the influence nil the semm lipids in mil. /'idlinin Arm Alt if. W>, 14 2, 1*1,9 Lewin, V., McKtain, W, A., and Wulfe, l:. II., Anile niftapeMlnncal i"'K')iv of 131 >T and ffll'ito mice nsine two nihcnh. M Fniinm (iinlfm 7'>.>ie/,. 4. 245. 1 *72 . Cle*. D. J., Lmbiyutosk-ily of chemical contaminant* of loods, T<khI (Vomer Xbvreof. 9.1*5.1*71 Knar. D. E, H., PetucUi- Index. College Science Fublnlim. Stair CnlkiK, fa.. 1*09. luchet, R V. and Crablica, D- C,, Handbook of luckily of pcslieidct lo wildlife. U S.111. Krani I'nhl. No 14, 1970. Kimbroufh, R. D., Lindti, R, F-, and Gaines, T. I., Morpbokipical chanpes In Itvm of lal* fed polyclikitinalrd biphenyls, Arch. 1'itnmii llulih, 25, 354, 1972. Plaitmow, N. S. and Karttad, L. II.. Dietary cffecli of polyclilorinalcd biphenyls nn mink. Can J Comp Med. 37.3*1, 1973 Ilealh, R. (!., Spann, J. W,, llifl, C. I ., and Kreitrer. J, K. Comparative dietary toxic diet of pesticide* In buds. Special Sc kiilifu Report Wildlife. U-S.l) I . No. I 52, 1*72 HID, K, F., Ilealh, K. II., Spann, i. W,, and Wliami, J. I)., Poiychhirinarcd hi|dienyl luckily lo iapanese quail as related lo deprec of ehl**rination, Fuvll Set, 53. 5*7. 1*74 Harris, J. R. and Rene, l...Toitniy of polychlorinated biphenyl* in poultry,J Ami. Tel. Med Attoe.. IAI. 1544. 1*72. Wildish, D. J., The loxkily t>r pnlyeltlorinated bipltenyti (fCIII in tea W4tct to Uamiuamt uccatueus. Bull T.nerron Contain, Toxicol. 5. 202. 1970. Hattnla, M, L. and Kartog. O., locniiy of pulychloiinaird biphenyls (fCHI lo pnldfiih. Aeta Niermarnl r*ictd. 31. 231. 1972 Ilanaen, D. J., farridt, f. R.. Lowe, J, I., Wilrum. A. J.. Jr., and Wihon. P. 11., Chronic loxhity, upralc <md reirntion of Aroehit 1254 in twoeiinartnc fnli. Hull Aiinimi Contain. Toinnf. h, 113. 1*71 Morgan,!. R., ITfetU nf Arochir 1242 la poiyiliiorinn ted lH|>hriiyll and 1)111 on cultures of an .ilpj. |>t,>i,>/<rji,. Uphnia, otlticod. and puppy. Bull. Airtwirn. (irniini, IrmVnl . 4. 12*. 1*72 Duke, T. W-, I owe. J, l,, and Witium. A. J.. Jr., A poly (hint iiialrd Inpheuyl lArmior 12541 in the isater. sediment, and bbtinf kuanbn Ray, I hind.,.Ilitll Aniirnn. (iaiMm. TrieiiiW.. 5. Ill, l*7U. Lkhlenrtein, k f., Schulr, X. R,, Tuhrmtiann, 1. W., and l.ianp. T. T.. Hkdopkal inlcraiikm between plasm um and inwethides. J Kffm. f.nromof . 52, 761, l*<>* Murtally, P., The cffccls of polychknobiphcnyls on Corthipput hnmiunt tSallalniia Acrididael, hmoitkd T.rp Appi. 12.206.1969. Bannctl, G. A., Drinker, C. X., and Warren, M. I;., klnrpholopieal ehanpes In the tirci* of rat* resuilinp from etpouire lo certain ehkirinated bydiocatboni./ htd IIi f Torirttl., 20,97.19)4. Ndhieumi, Liphl and eleclron mleioscopc Uudy of chkitohipbcnyl poltoninp in niouM and monkey liver. Are* frrwron Health.^21.620, 1*70. Kimbrough R. D,, Under, R. C., Rune, V. W., and Jcnniagi. R. W,, AdenofibiiKit in the ml liver, wilh pcrdUCKt at polychktrinnlcd biphenyls in adipose tissue, Arvli. t.iinnm Ihallh. 27. 3*0, 197 3 Rum, V. W,, Kknbron^i, R. 1)., VjHeneme, K. C.. Jr-ankip. R. W., Under. R. 1... and Soriscool W.. foiyehksrinated bipbonyls: tlniape, diilrihutinn, cterciion, and recovny. liver innrplmlrtpy afiei piolonpcil dietary Inpcslinn, Arc*, knrirmi Health. 29. 301.1 I* Aden, J. R. and Ahrahamaon, L. J., Morpt'-tlnpienl and hkiehemkal ehanpri in Ihe liver nT ran led polychlorinated biphenyls, Are*, ^.niirofl Confcm Toneol., 1.265. 1973 Ilanaell, M. M. and F.cobkhon. D. J., liffccli or ehcmkally pure chluriiliiphenyls on the morpholopy of rai liver. TiiMiml Appi Pharmacol.. 24.411.1974 Lilfant, C. L., farber, T. M.. Baker, A, M., and Van Limn, k. J., I'ifieci or poly ehknina ted biphenyls on hepatic miciotoma! anzymes in the rat, Toxicol. Appi. Iharmat ol. 23. 112. I *72 Uneer, I. L. and Peakall, D. B., Mctahnlic *Tfeels nr polyehlnrnialvd hiphrnyls in Ihe Amerk-an ketlrcl. Nature 22H. 74), 1970 Saptcmher 1*75 505 139. 1MV 161. 161. 161. 164. 165. 166. 167. 161. (69. 170. 171. 171. 171. 174. 175. 176. (77. 171. (79. ISO. 111. 111. 111. 114 115. Hi. 117. III. 119 190. 191. Cooney, A. H* Pharmacological implication* o( mkrniomal enrynic milui non. n,tnitm.nl (in', 19. 117, 1967. Cooney, A. M. and Iwm, J, J-> Metabolic imciiciiimi iimoni: t'lummmtnijl ikimrih and dnif*. A'icnrr, 171, 576, 1971, Abate*, A.F,,Ikiett,D.K.,Bnd Kappa*. A.,Polytlikwiiuiid biphenyls - am'*- typr orinducer of cytochrome p.44g 10 (be liver, /Tor. N*t< Acad. Sri US A.. 70, I 111, 1973. Chen, p, 9, Mehcndalt, H. M,, and I-udihetn, 1,,, t-rtiM >,r two isomeric letrachlori'hiplicnyl* on raisand thru hepatic enrytnet. Arch, Tmiron. Contain To.vnol. I, 36. 1973 Johnalone, C. I.. fcotmfcMt, 1>, I., end lluuinycr. O., The inllurine ol pure polychlorinated biphenyl compound* on hepatic leiHimn hi |hc ral, Toxicol Ap/4 Ihanoacol, II, 66.1474 Chen. 1. S, and Duhoii, K. P,, Studic* on (lie en/,yme inducing effect of polychlorinated biphenyl*, Toxnnl AppI Mttrmtcol.. 16. 504. 1973. Jicketi. D. 1C, llerher, I. C,, Kappa*. A., and Ahram. A, l\. Polychlorinated biphenyl*: comparative effrvn of high end hi* chlorine containing Arinkirr on hepatic mixed lumUon osmIju.-. Act Comtmm. Chnw, IVrhof. rtww,mo/. ), 505. 1971. Utter*), 1-. L. an# Van lav*. I- J,, l.oiyme induct inn by iiolyciiiorinatcd biphenyl* relative litkae9aiwltKvi| agcnli. ffor. Site, hxp Biol. Med. 141.765, 1971. galley. S. and hunyan, P, J., Interpretation uf persistence amt effect* of polychlorinated biphenyl* in bird*. Aterwrr. 116.14.1971 Nirvlcli, 11. G. and Norman, A. W,, I'nhiinci'd hepatic nwljIvtliMit <! InlintBuac. 4 andm*lme-3.l 7-daine. and csliudiol-l 7fl in chicken* prrHealed with Dili in PCh. Stcnmls. 14, *5, (971 Alice, K. S., and Plapp. F- Uf,, li., potychlorinatud hipltcnyh (I'CH al at indiHvr* nf mhn>*oinst enrynir activity in (he h<Hite fly, Arch. CnrimH Omtam. Toxicol., 1,111, 1973 VjHencuve, D. C., Oran(, D. L, rhillrp*. W, K. I., Clark. H. L.. and Clegg, D, J,. I.fleet* of PCB administration on microsomal enttynte activity in pregnant lahbiit. Bull, bit"iron. (iMim. Itanl, 6, (10. 1971. turner, J. C. and tircen, K. So The cfTect nf a polycWotmared tH|iheny( (Arnrlm 11541 un liver microsomal cnr.ymct in the male r(. Bull. Arnwrur. Contain. Toxical.. 11, 669.1974 Hart, t- G,, Shultrcr, A. W,, and Fool*. I. A.. Stimulatory effect* of chlnrdanr on hepalie microsomal drug mclabolitm in theral, Toxicol. Appt liiarmacol., 5,171, 1961. ViUcnenve, D. C., Craat, D. U, and FMIlipy. W. 1. I,, Modification uf pentobarbital deeping lime* In ran following chronic PCB inyc.iion. Butt, tuvinm. Contain. Toxicol., 7,164, 1971. PcpIS A. l_, Jr., Sanders, 0. T., and Kirkpalrtck, A. L., Acductiiin of pcntobarbilel-rnducrd decpiny lime* in PCtMiealcd rabbin.Ball. biirinm Contain Toxicol., II. 5IH, 1974 . VBIentuvr, D. C,, Gran) D. L, Kbcra. K., Clegg. IX J., Baer, It., and FhlHipt. W, f, J.. The feitiiuxitily of j polyvhtorinaled biphenyl mixture (Aroclor 1154) in (he rabbit and in Hie rat. lltyuol, 1,67, 1971, PeakeM, O I., lifted* of losepbenc on bepa lie cniy me induction and cnculjling tleioid level* in l|ie ia1. /.muon Health Penpeer., in pre**. 1975. Otberg. J. and Lundberg. C.. Some affect* of DDT and PCI! un I he hormonal tyiicm in Ihc male mou*c. tmirun WiyW. Biochcm., 4.116,1974. Paakall, O. I,, pjt'-DDT. effect on calcium metabolism and runcenlraliun nf etiiadtol in the bind, Irinnr, 161.591.1970 Morris, A. and PeakaH. D. unpubliibcd result*. 1975. Jefferies, D. J.. Induction of apparent hyperthyroidism in bird* ted OUT. Nailin'. 11. J7K, 1969. Keplinger, M. I-. Faneher, 0. K-, and Calandm. J, C., loiiciduyk iludie* with polychlorinated brphctiyli, BioArtl lAh. Bap., 197(1. Aularich. A. J,, Ainaar, A. K,, Seagnm, H. U, and Ynvalt. W. tl., lifleet* nf feeding robo *almon and other Crtai Lake* Oah on mink raprudonion. Can. J. Xool., 49. 611,1971. Amger, K. K,i Aniericb, A. i., and ZaMk, M., lifTcci* of dietary piOychluiinaied biphenyl* on growth and repioduclitm of mink. Am. Chrm, .W. Meet.. 11,149, 1971. Cooke. A.L, Shell thinnkng In avian egg* hy cnvirnnnicnlal putlulanls, Amir,in PoIIhi , 4.15,1973. Healh, R. G., Igattn, J, KtaiUet. J, F., and Vanea, C,, l.ffecl* tit pnlyctalutiiMicd biphenyl* on bod*, l.hh fat. OraMtol. Orngr . p. 475.1971. PcakaA, D- So KlTfeelt of potychliutnaied btfdwnyb IPCH"| on Hit rggitiHli uf riny. dove*. Ball, bnnron Ctmtam. Toxicol., 6. MK1,1971 Scotl, M. i~, Vadebri. D. V,, Mdhr niff, P. A,, Kimmey, (s U and Klee. A. Ur., Heoiliiof experiment* on Ihe effect* of PCS'*on laying hen pcri- .mancx, /Tor. fueriWf Nutr. Con]., p 56, 1971 Briihm. W. M. and Hneion, T. M,, Influence of polychlotinaled biphenyl* in ihc laying hen. iWl. Sit, 51, 1610, 1973. Lilie, R. J.. CccM. H. C,, Bilman. J., and Frka, G. I',, Uifleicncc* in icspouw of caged wbhr leghorn laycti to varioul polychhiriiialcd biphenyl* fPCB'a) in the diel.ftw/r. Set., 51.716,1974. Cactt, H. C,, Harria, S, J., Bilman, J., and Pftee, (1, l',, Potychhmnaied biphenylnndoi-Mf decteate in liver vitamin A in lapancte quail and rat*. Buff, fcrnvron. Contain. Toxicol. 9, 179. 1971. Dabtpen. A. B. and Under. R. U, tflccli of polychlorine led biphcnyU on pheataul reproduction, behavior and survival,/ Wild! Menage., 15,115, I97|. 606 CftC Critical hexicwt in knvironmcnlal Cimlrot .. HDMS *06864 ix: i, t 141 K, |4J ( T' 14* || |4(, |-t c (47 |l t4K I. <t 141 t I It lit I . V 'm r* i. < it r jn,i r \ 2i w i` r Jn5 x li i :<i7 ^ ii ) i i .Ml ^ i ite \ r 'l t Hr, i- :n i. in * i :i9 * ;.*ii * j.'i i i M I :;.t i i :.'4 k >. 7)7, 14*7 tnftrr 171, f cyiothiumc ialt and Ihcit tad biphenyl ayll, Toxicol live efleeii of "hem. Pthol town indueing cnylt in biidi. ,|7-dtone, and iryme Klnrity piiniilialiun on t mlaoaomal Ktowmal drug ; tima in tala -eping timet la hilntkily of a .*7.1971 etb in Ibc mi, nua K. lurhon Mood. Sfpfnee, aied biphenyh. and other Canal on giowtTi and Hi la on bhga, IJth i, Bull k'Hiiroh per(menu on the . Touli Set . 52. kpboin layaii In * la Inti kiiamin pun. bchavHH and 142. 191. 194 145 I9h 197. I9K 199. 2(k) 101 2712 2(13. 204 MS 2IKi 207 UK) 29 210 211. 212 212 214. 215 216. 217. lit. 219 220 221 222 221 224 lancet, I. L. Hit elli-cit nt ni|.pm.i1il`iiiins nn tlh- Aiiifiiuti IuMh'I i/pden vvrmniii Im.l Fbll Ibiuv t'mtirli (Inm-iMU.Ilh.ii.1. N V li?.' KikdtfitUfh. K. W., Palin [i1- <ii \hlmin.ii.il Imhneailain emitjiiiiiutimi m Men Zealand uibAntan Ih and tiMihil put ini hi nl' tinpiililislii d ihjiiiiiHii|>i. 1*175 |'(K. |>, J. ml llaf'i-U. B. I .. I it id dn tiluii anil If li'n ii(*iii tin- pi mini I kill pud mmiihulnyv i>t Jap.tune <|iMil rrii. M tnnrnn (tritium Immil. II 711. 1974 Hiiggt, 17. M. and ilirrin. J. K.. P.dyi hkniiuiid lupin-nils inUnetiic mi h.i1i'tijtfhis. Ptmh Xii 5J. 1291. Id7.1 flatunirw. N- S. ml Kridhiil, H Ilk' cues is oi |mpI>%lilmiiiali-il lii|i|k'iiy|p lArinhu 12547 iph illsi\-n ||-|' Ipi.kIih Ihui inlitny and hmih.iUln). (tn J Cnmft lli'd, .17. .Id 1, 147 V 47m J. (p.i I littiiiTiiJ-l ipI ITIli lif mammals jml tut Minis. /.rnpfitir I/ikIi/i riniPn'I.. I. |ll|. )47J lufllwnm*. C. i.. Bush. I., and Baker. 4. U.. If 'll h-sd- in fw yidks awhMIisI ullli nuhtuMt mi'll.>1Hi mid dflmlnitv nt hulilied shirks, tn/i l.imnui (imteiii limiii/, I. ,'IJ. I77.V tarlsnr, K. W. ml ITtlby. K. 7.. Ijnlvimnik i-lte.ts nl lluiv 17'H'i in Ihi- (kktM. M. f-.imnm I piiiiiiiii InUntl.. 4. Jhl. 747.1 W l.illic. R. I., lUrrik. S. I.. Cecil. II. I'., and Hitman, J.. Nntinal ie|trnJu.-ine pcrlntmaArrttfggalure cmln-ielt Ini Aim'll>1 I24K./Wl S<1. 51.1(414. 1474 : Plitunuw. N. S. and i'unnHI. II. S,, Annai'ilmr'enic-likc i-im i id tndubkiiiiulfd biphenyls in inili u l', I ri Mn . bK, Ul4, 1471 4`rcB. It Hitman. t. IdBic. R. J.. Ithn. Ci. I -, and Vrtrrll. J.. I ltd* ami I'Hh'kU hi uiibJtilH'i} IVftik' Irnnt hen* Ivd |f4yi|ilomiit|ii) hplirnvh lPtlWb|. tttViriUi (\mtot*i. /ivhi/, It 4719. 1914 PeakaH. D. II.. I.i*ii'i, J. I... and lllinim. S. I . I nihiyinik mmlatity and ilirmttnsniiul dlrulh'ni canted hi Aiochir 1154 in Tint' duvet. llirirnlt Ihulth h~rl(H t l , 1, 111,1, 1471 frakall. 17. H,, and PeakaH. M. 1.. I llm a |nilyi liktrnialeil Itt|4icm1 nil the irtMiHliHiinn nl mtilhi.ilU and naturally incululed dmv n>|fs. Z. d|i|d. I-.i iM . HI, Kh.l. 147.1 Knrhftrugh. R. W,, and Andrnim. 17. W,, J. Wihll limitgi . ill |*i-, 1475 Hitman. J. and leiil. (I. l.tlrii|-cmv activity nl 111)1' atulnrs and pnlyi'iilniinalcd biphenyls, J. /Itm l iaal (hrin ftwrif. IK, 11 UK. 147H. Ndan, J. A,. Minis nl dnli)m>><lipltcni |Ilull)*[m-tlk.nn' l|)1)1) atulnrs mid pidychlnrinalrd hipltcnyl tlVIll mlMllicsnn I7[M 'MtoiiadiiJ hiitduin I a iileiinc icirplnp, HuhIichi llwrllltit>l. 1.1,447. 1974 Jrrfctirk, t), J. and ParaMi*. J, I.. I ,, l.llssi nt' ntu- pnlyihimitkih'd lilplK-nyl on sj/t- and Jvln-iu nl iln cult Ihviiiid. Hull In in.in (tuiltm /ill* ill. K. HKi. 1971 JdTrrtca. D. J- and I rrnsh. M. C., Avbn Iliyiiinl 1-1 ii-i 1 nl Jill mi mu- and Ji itvin. ,Si ri if. i 117k l<>9 llutal. J, Cl.. Nrwi'mnrr. b, S., and Miitiisphi, J. A., Smin' i'lUsis nt l)l)| ii*va(ihi'iu and |mill, jil-r,n ii. j hijlllinyl nn tlinimt llinrlntn nl In-hwlllll-ipl.ld./`rlldf .Vu . 5.V 115. 1474 Mawa*. I- It.. Vilanlhi A: psilvnlial |nnin linn tinni i'aii'i|iny.i,ns. .Vui-inv. I Hi>, 71*, 1474 Jcffcrici. D. J. and l-n-m-h, M, C'.. Ilyprr and hypnlhyintahMU in |i|ftnKi ltd DIM; an i-spidiialitm lm the ihm iir*)i>>7* liheniimeimn. knrmm Mlui.. 1. 2 IS, 1471. Kiianra. N. T. and Balt*. T,, Nm|ilai>th' ehannes m the iat Inn indmvd l>y pnlyehliirinaU-J hipht-nyl. I .ami n4. 1115, 191 -V Nifutki, H-. TomH. S.. Mryt. T.. Marummi. M,, and Iln. R, IIl'paiiK'auiniici-niiMy ill Jkd\ihhirm.1 U'il bitilk-nyls in m*-c. liM. hi. KI75, 1972 Uehiyinia. M.. tTidia. 1'.. and Nnda, k.. I it-ia ri in. ip'iih i'l It-. 1 nl' 1)111 and IVH UWoip tin aw t h) It Itidait thimi-Hiduird iltrnik.al latimnrenesit. Hull l itnniii Cmtiain liiinnl . H.hHT. 1474. (icn, S.. ('aar, I. V,, Palmat. K, A., and On aid, l,, I Aik nl eyinyrnrlte flffili in hunt- mJin-k Jikl tprrmalnfimial irHs in tala iiralcd with p'dytbininuled biphenylt lAmelnu 1242 and 1254). tinII. l.mit,m PVtuunn. Miif.. 11,74. |47S l-tknd. M. and Trainett 17. 1),, PidyihToiinaicd hi|4H-ny1 inleraelinn ailli dnek he|miht s-lius. .Sm nu , |7il. 1.114. 1970 Vm, |. <t and dr Hni], | I inmuni IU1|I|'I l-tsiae atimilV lit .1 |m|\ tliliiMiijIed Ikithi-ntl iHepaialiiin mi HullumiuaLppninuni-ll-'t>iinte in rilinra )Hyt. 7i I unit .Ipfi/ /Tmpniui id . 21.544. 1472 Vlik, J. Si. and Ortrl-litinitcnhuin. I_ V., iy 'H iniluied tliinm-ttinn III Ihr luintmal and eell nirdtaled ptniiiiinil t an iruin fty-t. .S'ri hiltI l.tlilliilt . 1.2KV. 1472 Kidln. I_ 17. and 1 Tn^pcn, I. M, Hnvltenyl i \|iscd i dihnt, ,|m J I i i Kn, 14. Imi5. 147.) 7'nend, 74. and 1 taincii 17. O., Dusk lirpalilis vunt iiuerai linlit mill Dill and dirldtin in .nluli mall,nil'. Hull l.ttiiriui (twhtm hixiiol., 7, 2I)J, 1472 MiP unc. I.. 1... Saaayr. J. I ., and (7*t>rHi U. t... llydm (H-I h.iidmm and atellet in ehukt led a i hlmni.ili d hedineailiiin. 77hi/i .Si r., 4 7, 291. I9fi2 7-|itk, |7. I-.. IPlTcll, R, l|., and Ibdds. V. A,. .Sliiiln-i nt the elink edi-ina dik-pie, .1, huiiaiaiits nl timt.lmii, |ii.hIiiiell 7iy li-i-dme ehlniiiijlrd Tnidu'iiylt. 1`inill ,Vi. 44. 14lill. I`*i,i RchfrTd, H. M.. 77ladTry. R. I... Sundc. J.. and Sunde. M. I.. iiitnil) slndh't nn indyiblnaiiuied hifibemli > ih, t'hnk. h,ult Xu . 511. 1(191). 197! ' MONS 206885 i 115. lit. 11T. lit. 119. 1)0 1)1. 1)1. 13) . 134. 1)S. 134. 1)7. 1)1. 1)9. ' 140. 241. 141, 14) . 144. 24$. 146. 247. 24(. 249. 250. 251. Bayer, II. C. and Bird, F. H., Surface ehanyer in the epicardium nf chickens fed polvchkitinaied biphenyls. Awt< Sci.. 53,7)7. 1*74. Vos, I. G. Mid Iwniw. I. It., Cumpawlive iuxicrilueic.il study with potychkuinned biphenyls in chicken* with special reference to porphyria, edema formation, liver ntttmii and liisue residues. Tncrcof Appl Phtrmtrol IT.tSt. WO. Von, I. G., Van De Mot, II. L,, Ten Nucsrcr Dr kraurv, M. C.. and Dr Vos. R. H.. Identification and mikiilomal evaloaiion of chlorinated bibenrufurrn and chlorinated naptbalcnc in two commesial poll ' chlorinated biphenyls, hood felmrt Toxirol., It, US. 19*1 II Fircaronc, D., lirlnloiiy of chk-k edema disease. tmiraii. Wia/rt fwT/ari , 5. 59.197) Gilbertson, M.. and Fox, G.. unpublished rctulti. 1975 - Bowen, G W., Simonelt, k. R-. Borlinpeme. A, L., de Lappc. k, W., and RtarhnMifh. R. W.. The scauh for chlorinated dlbenroforani and chlorinated dibcnxodiuxini in wddtife populations ihuumy elevated levrls of embryonic death. Hmvimit Health Perxpeel.. 5. t9-i. 197) Voe, 1. G, klrkk, I. I. T. W. A,, Van Holsleyn, G W, M.. end Penninl*. J. It., Polychlorinated biphenyl* as inducers of hepatic porphyrh in Japanese quail, with special referenre tit s-ammolnrvtMr acid synthetase actlvily, fluorescence, and residues Hi the liver. Toxirol Appl Phtrnatol.. It). 1)1,1971. _ Dean, G.. Fwphyri*. Br. Med J. 1.1191.195). Vep, H. H., Dctaiah, D., end Cutkomp, I. K., Sensitivity of fiih ATPase* to pulysblnrlasted biphenyls. Ntiurc 111.61.1971. Desaiah, D., Cutkomp, L. K., Vep, H. H., and Koch, R. k-, Inhibition of ntipimpm inHiliK end -inscntitivi' matnesium edeauaine tiiphoaphalasc activity In fish by pulychlorinated biphenyls, BxKhem Phsrmtettl , 21. 157.1971. Koch, R. B., Dcsaleh. D., Vap, H. H,, and Cblkomp, L. K.. Folychkirinatcd biphenyls: effects of tonytrim exposure on ATPasc activity in fish. Pimrphtlei promekt. full. Inviroo. Conitm Toxicol., 7.17. 1971. Kinter, W. k., Merkens. L. S* lankki, R. H., and Cuarino. A. M,, Studies on the mechanism of toxicity uf DPT and polychktrmated btphenyh: disruption of oimorcyutatlor In marine fish. Anvinni Hrtllh ptnpcer. I. 169. 1971. Divts, P. W., Friedhoff, 3. M,, and Wedemtyer, C. A., Oipnitshlorinc insecticide. herbicide and pnlychlortnjied biphenyl (FOB) inhibition of NaK ATPase in rainbow trout. Bull fanrow. Coi/ram. TnxHid., 1.69, 1971. Sharp, C. W., Hunt, D, G., Cleavauls, S. T.,and Wilson, W. G., 11k influemc of dhhliudi|>hcnyltiichlioelhanr. polychlorinated biphenyls and anionk amphiphilic rompoundc on slabiliution of sodium- and potastiumactivaied adenosine triphosphatases by acidic phospholipids, Afof. Pharmacol, III. 119, 1974. Kek, I. L, Frteslet, L. -, and Sandiftr, S. H., Folychloiinaied biphenyl (Atodor Hall effects of uptake on yrowlh. nudeic acids, and chlorophyll of a marine diatom, Bull Krmron Coiittm Toxirol, 6. 156. 1971 Sodetften, A. end Svenssoa, k-, Uptake and accumulaliofl uf DDT and PCII by tphcmrra da,lire (Epbcmeroptcra) in costinunus-tluw systems. Bull imrntn. Contain. Toxirol. 9. 14). 197} Mosaer, 3. i_ FUret. N. S-, Tank TC., and Wunlat, C. F,, Folychlu,mated biphenyls: toxicity to certain phyiopUakiers. Science, 175,191, 1971. Moaaar, 3. U, Fhdsm, N. and Worster, C. F., Folychlorlnated biphenyls and DDT alter species composition in mixed cultures ofalpe,Setmcr. 176.533.1971. Wooer. 1. L. Tanf. T*C., Wallbar, W. G., and Wursler. C. F.. Inlciactron. of FCB s. DDT and DDK in a marine diatom, fuff. Atairon. Coman. Tbxtcof, 12,665, 1974 board, E. J., Sensitivity of DontUtll* and Srtntdrtmut (Chtorophyccac) to chlorinaled hydioraibotu. Phycotopa. 12, 29, 197). FUtes, N. S-, Graham. L, B-, Caepeater, E. )., and Warster, C. F-, Gaopraphk differences-in phylopiankton mnsipvsty to FCt s. Nature, 241, Sal, 197). Moore, S. A., Jt,, and Haniaa, R. Cn tfladr of polychlorinaled biphenyl on mi,me phytopbnklon communities. Ntiurt 240, )5(, 1972. Moors, 5. A., Jr., an4 Hvrin, R, Differential sensitivity to PCB by phytoplankton. War Mlul Buff.. 5.174. 1974. kkaa, J, R^ Abrdisasaon, L. I., aad Noeback. D. H., Riokmical effects pr potychlorinalcd biphenyl* and Irtphanyh on the subhuman primal*. Kuviron. Met . 6. 344. 1973 Allah, 1, IL, Noeback, D. H., and Hsu, 1. C,, 1 issue modifies'iuot in mimkeys as related to ahsnrplion. dHtribattoci, and excretion of pnlychlurinsled biphenyls. Arch Kncimu ((intern To.xutrl. 2. kb. 1974 Allan, J, R. and Noshack, p. H-, Ftdychlorinated biphenyl- and triphs-nyMnduced pitix mucosal hyperplasia in primates, Before*, 179,491,1973. Ahrahamaon, L J. and ABen, ). R-, The biotopicsl response of infant nonbuman prlmaies to a polychlorinaled biphenyl, hnvsron. Ilmhh Pmpttl., 4, It, 1973. - Pa*. ' Ill'S(its, ( t HlUVukl. Vi Km pc, It. Fitiiiun. it Mellunsci. I Mosscl, I) filih/i n Peakall, 1* Pitrouc. It RojJi. A Siii'lnii* S:miijij. M ScIisjI i /. V Siivcy. J I Vicls, ( t. Pape /'nr trpnii; llimun /', lnrii;nie A Ionizing M Ociurrcn. Mussel rCH's ntii! The Fnnr The Tt Hi The Tau, Urhon .Vi. llrhon Si , Urban .S,. Urban Si Water am,