Environmental Health Perspectives Supplements Vol. 102 Suppl 1:195-204 1994 Levels of Non-ortho-Subsituted (Coplanar), Mono- and Di-ortho- Substituted Polychiorinated Biphenyls, Dibenzo-p-Dioxins, and Dibenzofurans in Human Serum and Adipose Tissue by Donald G. Patterson, Jr., Glenn D. Todd, Wayman E. Turner, Vincent Maggio, Louis R. Alexander, and Larry L. Needham We have measured non-ortho-substituted (coplanar) polychlorinated biphenyl (PCB) levels as well as polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in human adipose tissue and serum collected in Atlanta, Georgia. The results show that the concentrations of the coplanar PCBs can be more than an order of magnitude higher than the concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Our measurements in pooled serum collected in 1962, 1988, and 1969 show a decrease in coplanar PCB levelsfrom 1982 to 1989. We found that the pattern of relative amounts of coplanar PCBs in adipose tissue varied greatly from person to person unlike the PCDD and PCDF patterns, which were more nearly the same. Age was significantly correlated with the concentrations of 2,3,7,8-TCDD,3,3'4,4'-PCB, 3,3',4,4A,5-PCB, and 3,3'4A,45,5'-PCB in adipose tissue. We also measured levels of the mono- and di-ortho chlorine- substituted PCBs in human serum. The levels for some of these PCB congeners were three orders of magnitude higher than the coplanar PCBs, PCDDs, and PCDFs. We used the international toxicity equivalency factors (TEFs) for PCDDs and PCDFs and the TEFs proposed by Safe for PCBs to calculate the 2,3,7,-TCDD equivalents. Four PCBs (3,3',4,4,5-; 2,3',4,4 A ,5-; 2,3,3',4,4'-; 2,3,3'4,4',5-) make a larger contribution than 2,3,7,&-?UD, while four other PCBs (3,3',4,4'5,5'-; 2,2;',3,4A,5'-; 2,2'A',f5,5 '-; 22',3AA',5,5 '-) make nearly the sane contribution as 2,3A7,$-?U)I The mono-orth-chlorine- substituted 2,3'4,4',5-PCB, however, is the major contributor to the total 2,V,78-TCDD equivalents in general population samples from the United States, Sweden, and Japan. The PCDDs are the second most significant contributor in the U.S. samples, whereas the coplanar PCBs are the second most significant contributor in samples from Sweden and Japan. Introduction Pblychlorinated biphenyl (PCBs) were produced in the United States under the trade name Aroclor and in Japan under the name Kanechlor. A variety of Aroclor and Kanechlor mixtures, which contain varying amounts of the 209 possible PCB congeners, were produced. Because ofthe widespread use of these mixtures, varying amounts of individual PCB congeners have been found in almost every area of the global ecosystem (1,2). The recent development of isomer-specific analytical methods (3) for PCBs Division of Environmental Health Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30333. Address reprint requests to D. G. Patterson, Jr., Mail Stop F17, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333. has allowed researchers to examine PCB mixtures for the non- ortho-chlorine-substituted biphenyls (coplanar PCBs) that are clearly the most toxic members of this class of compounds (4). A large part of Aroclor toxicity in animals has been associated with the coplanar PCBs, which are present in the mixtures in small amounts (3). Investigators have reported (5-7) that 3,3 '4'-tetrachlorobiphenyl [IUPAC number PCB-77 (8)],3,3', 4,4 '5-pentachlorobiphenyl (PCB-126), and 3,3',4,4 ',5,5 '-hexa- chlorobiphenyl (PCB-169) produce the following toxic and biological effects in some species of animals: body weight loss, dtymic atrophy, dermal disorder, hepatic damage, teratogenicity, reproductive toxicity, immunotoxicity, high binding affinity to hepatic cytosolic receptor protein (Ah receptor), and high induc- tion potency of 3-methylcholanthrene-type (3-MC-type) hepatic microsomal enzymes. A high level of induction of 3-MC-type hepatic drug metabolizing enzymes in rat hepatoma cell lines (9) PA7TERSONETAL. has also been attributed to mono-ortho-chlorine-substituted PCBs 2,3,3 4,4 '-(PCB-105), 2,3 '4,4 '5-(PCB-118), and 2,3,3 '4, 4 ',5-(PCB-156). Kannan et al. (3) found varying amounts of the coplanar PCBs in Aroclor and Kanechlor mixtures (Table 1). The highest con- centration in each mixture was PCB-77, followed by PCB-126 and trace amounts of PCB-169. Japanese researchers have since found these PCBs in terrestrial and marine animals such as dogs, cats, fish, porpoises, dolphins, and whales (10-12). Examples of the levels reported (13-19) are given in Table 2. In general, the same relative order of concentrations of the coplanar PCBs as are found in Aroclor and Kanechlor mixtures are found in these animals (PCB-77 >126 >169). Tanabe et al. (10) have found clear positive correlations be- tween concentrations of total PCBs and each of the three coplanar PCBs in all mammal samples analyzed (r=0.81-0.96 over a con- centration range of five orders of magnitude). These authors con- cluded that the sources of coplanar PCB contamination to the environment are principally from commercial PCB prepara- tions. Tanabe et al. (10) also reported that in fish samples, 95 % of the coplanar PCBs were PCB-77, 5% were PCB-126, and less than 1% were PCB-169 (this pattern is the same as in commer- cial PCB mixtures). Marine and terrestrial mammals, on the other hand, had a lower percentage of PCB-77, and the bioconcentration of PCBs-126 and 169 was obvious. The authors suggested that the concentrations of coplanar PCBs in humans and animals suggest that the order of biodegradability is PCB-77 > PCB-126 > PCB-169 (10). This order of metabolic stability is consistent with findings in studies of animals (20,21) and humans (22). Recent studies by Tanabe et al. (10,11,14,,23,24), Kannan et al. (12,25), Miyata et al. (26), and Kashimoto et al. (27) have found levels of PCB-77, PCB-126, and PCB-169 up to several orders Table 1. Coplanar PCB concentrations (ppm) in Aroclor and Kanechlor mixtures reported by Kannan et al. (3). PCB-77(%)a PCB-126 PCB-169 Aroclor 1242 5150 (0.5) 19.9 ND 1248 6060 (0.6) 62.3 ND 1254 601 (0.06) 46.0 0.66 1260 256 (0.03) 8.4 ND Kanechlor 300 4440 (0.44) 18.9 0.09 400 8500 (0.85) 89.3 0.57 500 1530 (0.15) 50.0 1.16 600 738 (0.07) 8.6 Trace ND, not detected. a Percentage of the PCB mixture. Table 2. Reported coplaner PCB levels (ppt) PCB-77 PCB-126 PCB-169 Reference Lake Michigan lake trout 3,500 1,500 NR (13) Killer whale 48,000 3,700 7,700 (14) Baltic herring 2,000-4,000 1,000-3,000 100-400 (15) Baltic herring and cod liver oil NR 20-50 NR (16) Baltic (Finnish) fish 70-900 30-300 NR (17) Pike muscle (Lake Kyrksjon) 77,000 6,500 420 (18) Striped bass (New York) 2-68,000 700-7,000 ND (19) Abbreviations: NR, not reported; ND, not detected. of magnitude higher than the levels of 2,3,7,8-tetrachlorodibenzo- p-dioxin (2,3,7,8-TCDD) in human adipose tissue samples from Japan. Noren et al. (28) reported high levels of these congeners in pooled mothers' milk from Sweden; Patterson et al. found them in pooled serum (29) and adipose tissue (30) from the United States, and Beck et al. (31) reported finding PCB-77 in adipose tissue and mothers' milk from Germany. We have ex- amined additional human adipose tissues and serum from Atlan- ta, Georgia, to determine the distribution of the coplanar PCBs, PCDDs, and PCDFs in these two lipid stores of the human body. Experimental The laboratory procedures we used to analyze polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and PCBs in adipose tissue and serum have been previously described in detail (29,32-37) and only a brief description will be given here. Sample Cleanup and Quantification We spiked the adipose tissue (32,33,36) or serum (29,34,35,37) samples with carbon-13-labeled PCDDs, PCDFs, and coplanar PCBs and in a separate analysis with carbon-13-labeled nonplanar PCBs. The separate analysis eliminated a previous problem with high recoveries of carbon-13-labeled PCB-77 (29). The samples were then ex- tracted with organic solvents, and the solvent extracts were pro- cessed through a five-column cleanup procedure developed by Smith et al. (38) and modified and semiautomated (33,39) by us for PCDD, PCDF, and PCB analyses. The final extracts were quantified by high-resolution gas chromatography/isotope- dilution high-resolution mass spectrometry for the PCDDs and PCDFs and by high-resolution gas chromatography/isotope- dilution high-and low-resolution mass spectrometry for the PCBs. Sample Procurement Pooled Human Serum. Serum collected by the Centers for Disease Control (CDC) blood bank in Atlanta, Georgia, was pooled and aliquotted into 100-g samples and stored at -600C until analysis. Collection of Adipose llssues. We collected adipose tissue samples at autopsy from the abdominal wall of men and women who died suddenly in Atlanta, Georgia, in 1984 or 1986. The samples were taken according to a specific protocol designed to ensure that the samples were not cross-contaminated or laboratory contaminated. The dead persons were from the general population in Atlanta, Georgia. Results and Discussion The levels that we measured for coplanar PCB-77, PCB-126, PCB-169, 3,4,4 '5,-PCB (PCB-81), mono- and di-ortho-PCBs, PCDDs, and PCDFs in pooled human serum and in adipose tissues collected in Atlanta, Georgia, are given in Tables 3-5. We measured 2,3,7,8-TCDD and coplanar PCB levels in 28 adipose tissue samples collected either in 1984 or 1986. The results given in Table 3 indicate that the concentrations of the coplanar PCBs 196 HUMAN LEVELS OF CHLORINATED DIOXINS, FURANS, AND BIPHENYLS TAble 3. Measured levels? of 2,3A7,-TCDD and non-ortho substituted PCBs in human adipose tissue collected from the general population in Atlanta, Georgia. Person Sample 2,3,7,8- PCB- PCB- no. Age Race Sex date TCDD PCB-77 126 169 PCB-81 1 39 B F 1984 2 68 B F 1984 3 57 W F 1984 4 35 W F 1984 5 76 B F 1986 6 35 W F 1986 7 55 W F 1986 8 30 W F 1986 9 48 W M 1984 10 69 W M 1984 11 19 B M 1986 12 25 B M 1986 13 28 W M 1986 14 27 W M 1986 15 51 B M 1986 16 71 W M 1984 17 75 B F 1984 18 19 B M 1984 19 67 B F 1984 20 56 B F 1984 21 67 B M 1984 22 78 B F 1984 23 63 W F 1984 24 46 W F 1984 25 53 B M 1984 26 28 B M 1984 27 48 B M 1984 28 45 W M 1984 3.1 22.2 12.5 9.0 38.0 4.6 8.3 9.2 3.0 8.5 3.0 1.6 2.6 3.2 6.8 19.4 13.6 10.2 13.2 9.4 8.4 24.3 9.2 11.6 13.8 10.6 7.8 5.3 Men Mean concentration 7.4 Range 1.6- b Mean age, 42.7 years 19.4 Women Mean concentration 11.6 Range 3.1- Mean age, 54.1 years 24.3 WomenC Mean concentration 13.4 Range 3.1- Mean age, 55.7 years 38.0 All Data Mean concentration 10.4 Range 1.6- Mean age, 49.2 years 38.0 2.8 11.7 11.9 9.6 16.7 4.3 20.8 NR 3.0 ND 9.4 6.4 4.0 2.6 7.8 11.3 23.6 5.7 19.1 11.3 27.9 9.1 15.9 25.0 19.4 19.3 10.9 6.9 9.6 ND- 27.9 13.8 2.8- 25.0 14.0 2.8- 25.0 11.7 ND- 27.9 66.7 36.7 NM 371 174 NM 299 56.7 NM 139 44.5 NM 263 118 NM 22.0 48.2 NM 106 96.5 NM 70.3 91.0 NM 14.6 34.2 NM 103 154 NM 33.7 69.9 NM 25.8 62.2 NM 18.0 34.5 NM 39.4 41.8 NM 61.5 112 NM 121 66.4 10.9 170 42.0 10.0 52.7 67.7 1.5 149 59.5 8.0 201 36.4 13.5 190 62.4 21.3 146 109 8.9 159 29.5 13.3 195 49.0 19.3 206 84.0 7.2 192 35.6 13.6 240 61.6 6.5 128 54.7 2.6 102 67.1 9.1 14.6- 34.2- 1.5- 240 154 21.3 161 67.1 12.2 22.0- 29.5- 8.0- 371 1748 19.3 168 70.8 12.2 22.0- 29.5- 8.0- 371 174 19.3 135 69.0 10.5 14.6- 29.5- 1.5- 371 174 21.3 Abbreviations B, black; W, white; F, female; M, male; NM, not measured; ND, not detected; NR, not reported. aLevels are in parts-per-trillion on a lipid-adjusted bases. bExcluding person 5, whose levels were obviously above normal U.S. background levels (40) c Including person 5. can be more than an order of magnitude higher than the concen- trations of 2,3,7,8-TCDD in human adipose tissue samples from the general population. In addition to measuring the coplanar PCBs, we measured the levels of all the PCDDs and PCDFs (Table 4) in the tissue of 5 of the 15 persons whose data are in Table 3. The mean levels of the PCDDs, PCDFs, and coplanar PCBs for these five are in Table 4. Data on subject 5 were exclud- ed from the calculation of the means since her levels were ob- viously elevated above normal U.S. background levels (40). We also measured PCB levels in pooled serum that was collected in Atlanta, Georgia, (Table 5). The coplanar PCB levels were similar in the 1988 and 1989 pooled samples, whereas the level of PCB-77 was three to six times higher in the 1982 pooled sam- ple. The levels of PCB-126 and 169 were about twice as high in TAble 4. Measured levels of PCDDs, PCDIR, and non-ortho substituted PCBs in human adipose tissue collected from the general population in Atlanta, Georgia. Person no.b Compound 5 6 7 11 12 MeanC 2,3,7,8-TCDD 38.0 4.6 8.3 3.0 1.6 4.4 1,2,3,7,8-PeCDD 38 8.5 12 16 10 11.6 1,2,3,4,7,8-HxCDD 18 3.7 5.3 NR 6.4 5.1 1,2,3,6,7,8-HxCDD 246 84 91 121 80.9 94.2 1,2,3,7,8,9-HxCDD 36 15 18 22 12.5 16.9 1,2,3,4,6,7,8-HpCDD 335 NR 48 NR 63.2 55.6 OCDD 2050 NR 396 NR 495 446 2,3,7,8-TCDF 0.8 0.7 1.8 1.1 0.7 1.1 2,3,4,7,8-PeCDF 13 3.3 4.3 3.9 3.4 3.7 1,2,3,,4,7,8-HxCDF 12 3.4 3.2 4.1 3.9 3.7 1,2,3,6,7,8-HxCDF 24 4.0 5.8 8.3 5.1 5.8 1,2,3,4,6,7,8-HpCDF 47.3 NR 8.9 NR 15.2 12.0 3,3',4,4'-PCB 16.7 4.3 20.8 9.4 6.4 10.2 3,3',4,4',5'-PCB 263 22.0 106 33.7 25.8 46.9 3,3',4,4',5,5'-PCB 118 48.2 96.5 69.9 62.2 69.2 Abbreviations: CDD, chlorinated dibenzodioxin; CDF, chlorinated diben- zofuran; T, tetra; Pe, penta; Hx, hexa; Hp, hepta; 0, Octa; NR, not reported. aLevels are in parts-per-trillion on a lipid-adjusted basis. bThese persons are the sane as those descibed in Table 3. cThis mean concentration excludes person 5, whose levels were above nor- mal U.S. background levels (40). the 1982 pooled sample. These data are consistent with a decrease in human exposure to PCBs and a shorter half-life in humans for PCB-77 than for PCBs-126 and 169. The only data reported in the scientific literature on levels of PCDDs, PCDFs, and PCBs with which we can compare our results are given in Table 6. These data should be compared with caution, however, because the U.S. (29), Japanese (10,25-27), and Swedish (28,41) samples represent people with different background exposures and were not collected to represent a cer- tain population group. In addition, individual PCB congeners (42,43) as well as total PCBs (44-46) have been shown to be pos- itively associated with age; differences between the sexes have also been noted (43,46). The studies in Table 6 representcohorts with different mean ages and varying male-to-female ratios. Toxic equivalency factors (TEFs) have been developed for the various congeners of PCDDs, PCDFs, and PCBs (4,47). The TEF scheme compares the in vivo and in vitro responses of some species of animals to various congeners relative to that of 2,3,7,8-TCDD (Table 7). In deriving the TEFs (44), data from the following effects were used in descending order of priority: results of long-term carcinogenicity studies; data from reproduc- tive studies; results of subchronic experiments that measure Ah receptor-mediated responses such as thymic atrophy, body weight loss, and immunotoxicity; acute toxicity studies; and in vivo or in vitm biochemical responses such as enzyme induction or receptor binding (4). A complete set of data that included long-term carcinogenicity studies was available only for 2,3,7,8-TCDD, and therefore the TEFs assigned to other con- geners were subjective assessments made by using the above priorities as a guide (4). The 2,3,7,8-KDD equivalents have been calculated for data in all studies available for comparison and are given in Table 6 along with the percentage of the total 2,3,7,8-TCDD equivalents for PCDDs, PCDFs, and coplanar PCBs. Figure 1 is a comparison of studies that measured all three compound classes in each 197 PA77ERSONETAL ?hble 5. Measured levels of 2Z3,7,8TCDD, non-ortho, mono-orlo, and di-orihoPCBs in pooled human serum.a Serum pool 1 Serum pool 2 Serum pool 3C (100 g samples) (50 g samples) (10 g samples) nC Mean ? SD CV n Mean ? SD CV n Mean ? SD CV 2,3,7,8-TCDD 101 0.159 ?0.0241 15.1 84 0.0165 ?0.0027 16.7 - NM - 3,3',4,4'(77) 3 0.481 ? 0.0762 15.8 6 0.251 ?0.0453 18 3 1.38 0.15 10.8 3,3',4,4',5(126) 3 0.183 ?0.0203 11.1 6 0.135 ?0.0233 17 3 0.281 0.0577 19.5 3,3',4,4',5,5'(169) 3 0.151 ? 0.0103 6.8 6 0.192 ? 0.0491 25.5 2 0.282 - 2,3,3',4,4'(105) 4 33.2 ? 19.2 5.3 - NM - - NM - 2,3',4,4',5(118) 4 366 ? 1.8 5.4 - NM - - NM - 2,3,3',4,4',5(156) - NM - - NM - - NM - 2,2',3,4,4',5'(138) 4 583 ? 33.0 5.7 - NM - - NM - 2,2',4,4',5,5'(153) 4 690 ? 60.4 8.7 - NM - - NM - 2,2',3,4,4',5,5'(180) 4 466 ? 24.0 5.2 - NM - - NM - Total PCBs 4 3,100 ? 270 8.7 - NM - - NM Abbreviations: NM, not measured; CV, coefficient of variability. aLevels in parts per trillion on a whole-weight basis. bPooled human serum (total lipid = 475.3 mg/dL) collected in 1988 from more than 240 donors. This pool has been spiked to a higher level with 2,3,7,8-TCDD (see Table 6 for levels on a lipid-adjusted basis). CThe number of repeat analyses on the same pool. dThis pool is of unspiked, normal human serum collected in 1989 from more than 200 donors. eThis pool is of unspiked, normal human serum collected in 1982 from more than 200 donors. Table 6. Reported levels and 2,3,7,8-TCDD equivalents of PCDDs, PCDFs, and PCBs in human adipose tissue, mothers' milk, and serum.3a Japan Sweden USA Adipose tissue, Adipose tissue, Adipose tissue, Breast milk, Breast milk, Serum, lipid Adipose tissue, Adipose tissue, wet/weight wet/weight (26)c lipid adjusted lipid adjusted lipid adjusted adjusted lipid adjusted lipid adjusted' (10,25) (27)d (28)e (41 )f (29)9 (this study)h 2,3,7,8-TCDD 9.6 (9.6) 1.2 (1.2) 5.5 (5.5) 3 (3) 1.9 (1.9) 3.6 (3.6) 4.4 (4.4) 10.4 (10.4) 1,2,3,7,8-PeCDD 15.9 (7.95) 11.9 (5.95) 12.3 (6.15) 7 (3.5) 3.4 (1.7) NR 11.6 (5.8) NR 1,2,3,4,7,8-HxCDD 8.1 (0.81) -J -4i _ NR 5.1(0.51) NR 1,2,3,6,7,8-HxCDD NR 68 (6.8)i 79.5 (7.95)i 38 (3.8)i 18.5 (1.85)i NR 94.2 (9.42)J NR 1,2,3,7,8,9-HxCDD NR _J -4 -i 4.2 (0.42) NR 16.9 (1.69) NR 1,2,3,4,6,7,8-HpCDD NR 28.5(0.28) 62.1 (0.62) 57(0.57) 37.3(0.37) NR 55.6(0.56) NR OCDD 251 (0.25) 830 (0.83) 1,327 (1.33) 268 (0.27) 173 (0.173) NR 446 (0.45) NR Total 285 (18.6) 940 (15.1) 1,486 (21.6) 373 (11.1) 238 (6.4) - 634 (22.8) % Total of TEq 24 13.8 33.7 22.5 - 66.9 2,3,7,8-TCDF 9.4 (0.94) NR 3.6 (0.36) 2 (0.2) 1.3 (0.13) NR 1.1 (0.11) NR 2,3,4,7,8-PeCDF 29.1 (14.6) NR 23.2 (11.6) 17 (8.5) 7.1(3.55) NR 3.7 (1.85) NR 1,2,3,4,7,8-HxCDF 14.9 (1.49) NR i i 2.8 (0.28) NR 3.7 (0.37) NR 1,2,3,6,7,8-HxCDF 14.9 (1.49) NR 26.3 (2.63)9 7 (0.7) i 2.2 (0.22) NR 5.8 (0.58) NR 1,2,3,4,6,7,8-HpCDF NR NR 11.3 (0.11) 8 (0.08) 4.3 (0.043) NR 12.0 (0.12) NR OCDF NR NR 5.8 (0.01) 2 (0.002) 1.7 (0.002) NR NR NR Total 68.3 (18.6) - 70.2 (14.7) 36 (9.5) 19.4 (4.2) - 26.3 (3.03) % Total of TEqk 24 - 9.4 28.7 14.8 - 8.9 - PCB 77 348 (3.48) 39 (0.39) 173 (1.73) 27 (0.27) 20.7 (0.21) 104 (1.04) 10.2 (0.10) 11.7 (0.12) PCB 126 324 (32.4) 250(25) 1,002(100.2) 98(9.8) 152 (15.2) 39.5 (3.95) 46.9 (4.69) 135 (13.5) PCB 169 89.5(4.48) 132(6.6) 356(17.8) 47(2.35) 49.2(2.46) 32.6(1.63) 69.2(3.46) 69.0(3.45) Total 762 (40.4) 421 (32) 1,531 (120) 172 (12.4) 222 (17.9) 176 (6.6) 126 (8.25) 181 (13.6) % Total of TEq 52 - 76.7 37.6 62.7 - 24.2 - PCB 118 (ppb) 91 (91) NR NR 25.4 (25.4) NR 79 (79) NR NR PCB 105(ppb) 25(25) NR NR 6.5(6.5) NR 7.2(7.2) NR NR PCB 156 (ppb) 20 (20) NR NR 14.3 (14.3) NR NR NR NR PCB 138 (ppb) 200 (4) NR NR 116 (2.32) NR 126 (2.52) NR NR PCB 153 (ppb) NR NR NR 151 (3.02) NR 149 (2.98) NR NR PCB 180 (ppb) NR NR NR 64.4 (1.29) NR 101(2.02) NR NR Abbreviations: CDD, chlorinated dibenzodioxin; CDF, chlorinated dibenzofuran; T, tetra; Pe, penta, Hx, hexa; Hp, hepta; 0, Octa; NR, not reported. aLevels in parts per trillion [values in parenthesis are 2,3,7,8-TCDD equivalents (4,47) see Table 7]. bTissue collected in 1985 from 12 cancer patients in Matsuyama, Japan. CTissues collected in 1986 from two persons who died suddenly in Osaka City, Japan. dTissues collected in 1986-1987 from 39 persons who died suddenly in Osaka, Nara, and Okinawa prefectures in Japan. ePooled milk collected in 1988-1989 from Stockholm, Sweden. fPooled breast milk collected in 1988 from Sweden. gPooled serum collected in 1988 from Atlanta, Georgia (see Table 5). hData from the present study. Tissues collected in 1986 from four perons who died suddenly in Atlanta, Georgia (data from Table 4). 'Tissues collected in 1984 and 1986 in 28 persons who died suddenly in Atlanta, Georgia (data from Table 3). JThese congeners reported as a sum of HxCDDs or HxCDFs. kPercent of the total 2378-TCDD equivalents for PCDDs, PCDFs, and coplaner PCBs. 198 HUMAN LEVELS OF CHLORINATED DIOXINS, FURANS, AND BIPHENYLS Table 7. Toxicity equivalency factors CrEFs) for PCDDs (47), PCDFs (47), and PCBs (4). Congener TEF 2,3,7,8-TCDD 1.0 1,2,3,7,8-PeCDD 0.5 1 ,2,3,4,7,8-HxCDD 0.1 1 ,2,3,6,7,8-HxCDD 0.1 1,2,3,7,8,9-HxCDD 0.1 1,2,3,4,6,7,8-HpCDD 0.01 OCDD 0.001 2,3,7,8-TCDF 0.1 2,3,4,7,8-PeCDF 0.5 1,2,3,7,8-PeCDF 0.05a 1 ,2,3,4,7,8-HxCDF 0.1 1,2,3,6,7,8-HxCDF 0.1 1,2,3,7,8,9-HxCDF 0.1 2,3,4,6,7,8-HxCDF 0.1 1,2,3,4,6,7,8-HpCDF 0.01 a 1,2,3,4,7,8,9-HpCDF 0.Ola OCDF 0.001 3,3',4,4'-PCB (77) 0.01 3,3',4,4',5-PCB (126) 0.1 3,3'4,4',5,5'-PCB (169) 0.05 Mono-ortho-substituted PCBs 0.001 Di-ortho-substituted PCBs 0.00002c Abbreviations: CDD, chlorinated dibenzodioxin; CDF, chlorinated diben- zofuran; T, tetra; Pe, penta; Hx, hexa; Hp, hepta; 0, octa. 2Safe has proposed 0.1 (4). bA highly conservative value according to Safe (4). CRecommended as a preliminary value until more data can be acquired for these PCBs (4). sample for each person. The reported levels in adipose tissue col- lected in 1985 and 1986 from Japan show that most of the 2,3,7,8-TCDD equivalents are due to the coplanar PCBs. Pooled mothers' milk collected by Noren (28) in 1988 and 1989 in Stock- holm, Sweden, has nearly equal percentages of 2,3,7,8-TCDD 90. PCDDs 60 2 14ll 6- 52 45- 30- ~ 24 24 I ki 0 1 18.6 18.5 40.4 2,3,7,5 TCDD TANABE/KANNAN (10,25) EQUIVALENTS ADIPOSE TISSUE JAPAN, 1965 equivalents due to PCDDs, PCDFs, and coplanar PCBs. The majority of the 2,3,7,8-TCDD equivalents in adipose tissue col- lected in 1986 from Atlanta, Georgia, are due to the PCDDs (67%), whereas the coplanar PCBs account for the second highest percentage (24%). Measurements in pooled mother's milk by Thornburg (21) collected in 1988 from Sweden indicate that 63 % of the 2,3,7,8-TCDD equivalents are due to the coplanar PCBs. The differences between our results in adipose tissue (Figure 1) and the results from the studies in Sweden and Japan could be due to several factors: a) different matrixes; b) different mean ages; c) different sample collection years from different countries [the data of Patterson et al. (48) and Stanley et al. (49) indicate that PCDD and PCDF levels may be decreasing in U.S. serum and adipose tissue, and the data of Noren et al. (28) show that levels of PCDDs, PCDFs, and coplanar PCBs decreased from 1972 to 1985 in pooled mothers' milk in Sweden]; d) our adipose tissue levels were measured in men and women, but the mothers' milk levels were measured in women who may have been breastfreding infants when the samples were collected [breastfeeding may have altered the normal PCDD, PCDF, and PCB patterns]; and e) different background exposures to PCDDs, PCDFs, and PCBs in the United States, Japan, and Sweden. The levels and 2,3,7,8-TCDD equivalents of 2,3,7,8-TCDD and coplanar PCBs that we found in the adipose tissue of men and women from Atlanta, Georgia, are compared in Table 8 to those reported by Tanabe (24) and Kanman (25). In the U.S. samples, women had higher levels of each analyte, whereas men had higher levels in the Japanese samples. The number of samples in both of these studies is, however, too small to make statistically significant statements concerning the observed differences. The patterns of coplanar PCB levels in adipose tissue also ap- pear to be different for men and women in the Atlanta samples PCDFs E COPLANAR PCBs 21.b 14.7 12U 22.8 3.U 8.3 b.41 4.2 17.9 11.1 9.5 12.4 KASHIMOTO (27) PATTERSON (Present Study) THORNBURG (41) NOREN (28) ADIPOSE TISSUE ADIPOSE TISSUE POOLED BREAST MILK POOLED BREAST MILK JAPAN, 1986 USA, 1986 SWEDEN, 1966 SWEDEN, 1988/1989 FIGURE 1. Percentage of total 2,3,7,8-TCDD equivalents for general population samples. 199 PA77ERSONETAL. Table 8 Reported mean levels and 2,3,7,8-TCDD equivalents? of the 2,3,7,8TCDD and coplanar PCBs in adipose tissue collected in 1985 in Matsuyama, Japan, and in 1986 in Atlanta, Georgia. Present study Tanabe (24) and Kannan (25) 14 Men (mean 13 Women 7 men (mean 5 Women (mean age=43) (mean age=54) age=59) age=59) 2,3,7,8-TCDD 7.4(7.4) 11.6(11.6) 11 (11) 7(7) PCB-77 9.6 (0.096) 13.8 (0.14) 400 (4) 270 (2.7) PCB-126 102(10.2) 161 (16.1) 400(40) 240(24) PCB-169 67.1 (3.35) 67.1 (3.35) 120(6) 53(2.6) aLevels in parts per trillion. Values in parenthesis are 2,3,7,8-TCDD equivalents based on data in Safe (4) and NATO (47). ADIPOSE TISSUE B JAPAN (1025) ii.~~ D 77 126 169 ADIPOSE TISSUE Japan (26), C USA (Present Study) POOLED PLASMA m Sweden (Present Study) 77 126 169 ADIPOSE TISSUE IL JAPAN (10,25) POOLED SERUM USA (Present Study) 77 126 169 ADIPOSE TISSUE JAPAN (26), USA (Present Study) POOLED BREAST MILK Sweden (28), jlSWEDEN (41) 77 126 169 FIGURE 2. Coplanar PCB patterns in human samples. (Table 3). The level of PCB-126 is the highest of the three coplanar PCBs in 12 of the 14 women and PCB-169 is the highest in 8 of the 14 men (the number of individual samples is too small to establish a definite pattern difference). Within a group of nor- mal population samples, the reported pattern of PCDDs and PCDFs is ususally the same. The absolute levels may vary from person to person, but the relative amounts of the various con- geners are generally the same (for example, see Table 4). This similarity of pattern is not true for the coplanar PCBs. The various patterns of the coplanar PCBs that have been reported are shown in Figure 2. Tanabe and Kannan (10,25) found patterns A and B (Fig. 2) in adipose tissue from Mat- suyama, Japan, but Miyata et al. (26) found patterns C and D (Fig. 2) in adipose tissue from Osaka City, Japan. We also found patterns C and D (Fig. 2) in adipose tissue and pattern B (Fig. 2) in serum from Atlanta, Georgia. We measured coplaner PCB levels in a pooled plasma sample that was collected from Sweden as part of a World Health Organization (WHO)-sponsored laboratory round-robin study of PCDDs, PCDFs, and PCBs (50). We observed pattern C (Fig. 2) in this pooled plasma sam- ple. Pooled mothers' milk collected in Sweden (28,41) exhibited pattern D (Fig. 2). These variable patterns may be caused by dif- ferent dietary habits (N. Kannan, personal communication), by different metabolic elimination rates, or by different routes of exposure. We have calculated Pearson correlation coefficients and pro- bability values (Table 9) for the coplaner PCB and 2378-TCDD data from Table 3. There are statistically significant correlations Table 9. Pearson correlation coefficients between concentration of individual coplanar PCB congeners and 2,3,7,-TCDD and age in adipose tissue obtained at autopsy from 28 persons from Atlanta, Georgia. 2,3,7,8-TCDD PCB-77 PCB-126 PCB-169 Age 2,3,7,8-TCDD 1.000 - - - 0.667 (0.0001) PCB-77 0.365 1.000 - - 0.409 (0.061)a (0.034) PCB-126 0.647 0.540 1.000 - 0.579 (0.0002) (0.0037) (0.0013) PCB-169 0.511 -0.054 0.334 1.000 0.411 (0.0054) (0.788) (0.082) (0.030) aProbability values in parenthesis. between the levels of 2,3,7,8-TCDD and PCB-126 and -169, as well as between PCB-77/126. Age was significantly correlated with concentration for 2,3,7,8-TCDD, PCB-77, PCB-126, and PCB-169 (Table 9). Luotamo et al. (51) found good correlations in paired serum and adipose tissue specimens only for the bioac- cumulating, slowly metabolized PCB congeners. The lack of a good correlation between PCB-77/169 and PCB-126/169 in our study is consistent with Luotamo's findings. Our serum data (Table 5) for 1982 and 1988/1989 suggest a shorter half-life for PCB-77 relative to PCB-126 and 169 and is consistent with a study in mice that showed that PCB-126 was more slowly metabolized than PCB-77 (52). The bioconcentration of PCB-126 and 169 is also clearly seen by comparing the relative levels in the human exposure sources (Aroclors and Kanechlors, Table 1) to the relative amounts found in human tissues (Table 6). In Figure 3, we compare the levels of mono- and di-ortho- substituted PCBs in pooled serum samples taken in Atlanta in 1988 (29) with the levels in serum samples taken in 1986 from 200 Wisconsin consumers of sport fish (53); serum samples taken in 1988 from 19 Columbia, Missouri, residents (54); pool- ed serum taken in 1990 from Finland (55); and pooled serum taken in 1990 from Quebec, Canada (56). The relative amounts of the various PCB congeners were similar in our pooled serum and the Columbia, Missouri, residents(54), as well as in pooled serum from Canada (56). The mean levels for the three major di- ortho-substituted PCBs [2,2 ',3,4,4 ',5 '-(PCB-138); 2,21'4,4 '5,5 '-(PCB-153); 2,2'3,4,4 '5,5 '-(PCB-180)J and the ma- jor mono-ortho-substituted PCB-118 were higher by a factor of about two in the Wisconsin samples than in the Atlanta pooled serum. The differences in PCB levels may be due to the high fish consumption among persons who provided the Wisconsin samples (53). Fiore et al. (57) have found statistically significant positive Spearman correlations between sport-caught fish meals and PCB serum levels. Humphrey (58) has reported that, among Michigan residents, increased fish consumption correlated positively with increased PCB concentrations in serum. Figure 4 shows the results of six studies with data on mothers' milk, adipose tissue, and lipid-adjusted serum levels of mono- and di-ortho-substituted PCBs. Although the absolute amounts of the individual PCB congeners vary among studies, the relative distribution patterns of the PCB congeners within each study are similar. In addition, the di-ortho-substituted PCB levels are higher than the mono-ortho-substituted levels, which are in turn higher than the coplanar PCB levels (Fig. 4, Table 6). A 200 HUMAN LEVELS OF CHLORINATED DIOXINS, FURANS, AND BIPHENYLS 1,500 WEBER (56) POOLED SERUM PATTERSON(2 QUEBEC, CANADA ATLANTA, GA. * LUOTAMO (55) POOLED SERUM M SONZOGNI (53 CJ_ FINLAND WIISCONSIN, U cn) g YANDERS (54) SERUM (n. 19) COLUMBIA, MO. USA co I- 0. 500- 366 3 FIGUREO3 Mo - ad t i nse 105 11E FIGURE 3. Mono- and di-ortho-substituted PCBs in human serum. 0 C/3 Cl 0- -J w 0 - Co IU cn- 0.. 3 156 138 153 180 PCB CONGENER 350 300 250 200 150 100 50 0 FIGURE 4. Mono-and di-ortho-substituted PCBs in human serum, breast milk, and adipose tissue from general population samples. 1P18 105 156 138 153 180 PCB-CONGENER 201 202 PATTERSONETAL. I V POMSN P MED WMCOLLECTED I"b IN1NFO TWA A n 9 * NORENI2)(POOLEDBREAST MILKCOI.ECTED IN 19gW1 FROMSTOc1 KLSWEDESo T* BE (I. 2qA OPOSE TISSUE COLLECTEDH 1N FROINS FM MAGIJAMJA 32 !Z- ~~~~~~~~~~~~~~~~~~~~~~~~~~20 -J 14 0 10 9.6 9.6 2,3,7,8-D 77 126 169 118 105 156 138 7.2 4 .5 &~ 3 3 2 1.6~~~~~~~~~~~~~~~~~~~~~~~~~~~. 1~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. 2,317;8-D 77 126 169 118 105 156 138 153 180 CHLORINATED CONGENER FIGURE 5. 2,3,7,8-TCDD equivalents for 2,3,7,8-TCDD, coplanar PCBs, and mono-and di-ortho substituted PCBs from general population samples. Table 10 Total 2,3,7,8-TCDD equivalents in various countries for PCDDs, PCDFs, coplanar PCBs, and mono- and di-ortho substituted PCBs. United States (prensent study) Sweden (28) Japan (JG) PCBs-118,105,156 86.2 (68)a 46.2 (54) 136 (62) PCBs-138,153,180 7.5 (6) 6.6(8) 4 (2) PCBs-77,126,169 6.6 (5) 12.4 (14) 40.4 (19) PCDDs 22.8 (18) 11.1 (13) 18.6 (8) PCDFs 3.0 (2) 9.5 (11) 18.6 (8) percent of the total 2,3,7,8-TCDD equivalents in parentheses. The 2,3,7,8-TCDD equivalents for 2,3,7,8-TCDD, coplanar PCBs, mono- and di-ortho-substituted PCBs from serum (29), mothers' milk (28), and adipose tissue (10,25) are compared in Figure 5. Clearly, each of the coplanar PCBs, and mono- and di- ortho-substituted PCBs makes a major contribution to the total 2,3,7,8-TCDD equivalents in these general population samples. In fact, PCBs-126, 118, 105, and 156 all make a larger contribu- tion than 2,3,7,8-TCDD, while PCBs-169, 138, 153, and 180 make nearly the same contribution as 2,3,7,8-TCDD. The major con- tributors, however, to the total 2,3,7,8-TCDD equivalents in samples from the United States, Sweden, and Japan (Table 10) are the mono-ortho-chlorine-substituted PCBs 105, 118, and 156 (within this group, the PCB 118 was by far the major contributor: see Fig. 5). The coplanar PCBs were the second most important contributor in the Swedish and Japanese samples, whereas the PCDDs were the second most important in the U.S. samples. Undoubtedly, more and more measurements of PCBs in en- vironmental and biological specimens will be done by congener- specific methods. In the United States, however, regulatory agencies such as the Food and Drug Adminisration, En- vironmental Protection Agency, and Department of Agriculture have established guidelines and analytical methods (based on packed-column gas chromatography) for total PCBs, not for in- dividual congeners (60,61). In Europe, PCB levels are frequently regulated on the basis of the concentration of five or six PCBs that are normally found at the highest relative levels. Certainly, more comparisons, such as those performed by Burse et al. (62), need to be made between results of packed-column and capillary- column methods. More specifically, however, future work will be based on methods that involve capillary-column gas chromatography/mass spectrometry and allow identification and quantification of coplanar PCBs and other PCBs that, although minor in concentration, greatly contribute to the 2,3,7,8-TCDD equivalents. For human studies, we need more work on exposure assessment, half-lives, partitioning within the body's compart- ments, and assessments of any adverse health effects that these coplanar PCBs alone or in combination with other environmen- tal contaminants may cause. Use of trade names is for identification only and does not constitute endorse- ment by the Public Health Service or the U.S. Department of Health and Human Services. REFERENCES 1. Bellschmiter, K., Buchert, S. H., Zell, M., Figge, K., Pblzhofer, K., Hoerschelman, H. Studies ofthe global baseline production, V., Monitoring the baseline pollution of the subantarctic by penguins as bioindicators. Fresenius' Z. Anal. Chem. 309: 1, 1-7 (1981).. 2. Kimbrough, R. D., Ed. Halogenated Biphenyl, Terphenyls, Naphthalenes, Dibenzodioxins and Related Products. Elsevier, New York, 1980, p. 406. 3. Kannan, N., Tanabe, S., Wakimoto, T., Tatsukawa, R., Coplanar HUMAN LEVELS OF CHLORINATED DIOXINS, FURANS, AND BIPHENYLS. 203 polychlorinated biphenyl in aroclor and kanechlor mixtures. J. Assoc. Off. Anal. Chem. 70: 451-454 (1987). 4. Safe, S. Polychlorinated biphenyl, dibenzo-p-dioxins, dibenzofurans, and related compounds; environmental and mechanistic considerations which support the development of toxic equivalency factors. CRC Crit. Rev. Tox- icol. 21: 51-88 (1990). 5. Poland, A., and Glover, E. Chlorinated biphenyl inductionofaryl hydrocar- bons hydroxylase activity:a study ofthe structure activity relationships. Mol. Pharmacol. 13: 924-938 (1977). 6. Safe, S. Polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBB): biochemistry, toxicology and mechanism of action. CRC Crit. Rev. Toxicol. 13: 319-395 (1984). 7. Leece, B., Denomme, M. A., Towner, R., Angela, L. S. M., and Safe, S. Polychlorinated biphenyl: correlation between in-vivo and in-vitro quan- titative structure-activity relationships (QSARs). J. Toxicol. Environ. Health 16: 379-388 (1985). 8. Ballschmiter, K., and Zell, M. Analysis of polychlorinated biphenyl by capillary gas chromatography. Frens. J. Anal. Chem. 302: 20-31 (1980). 9. Parkinson, A., Safe, S., Robertson, L. W, Thomas, P. E., Ryan, D. E., Reik, L. M., and Levin, W. Immunochemical quantitation of cytochrome P-450 isozymes and epoxide hydrolase in liver microsomes from polychlorinated or polybrominated biphenyl-treated rats. J. Biol. Chem. 258: 5967-5976 (1983). 10. Tanabe, S., Kannan, N., Subramanian, A., Watanabe, S. Tatsukawa, R. Highly toxic coplanar PCBS: occurrence, source, persistency and toxic im- plications to wildlife and humans. Environ. Pollut. 47: 147-163 (1987). 11. Tanabe, S., Kannan, N., Wakimoto, T., and Tatsukawa, R. Method for the determination of three toxic non-ortho chlorine substituted coplanar PCBs in environmental samples at parts per trillion levels. Int. J. Environ. Anal. Chem. 29: 199-213 (1987). 12. Kannan, N., Tanabe, S., Ono, M., and Tatsukawa, R. Critical evaluation of polychlorinated biphenyl toxicity in terrestrial and marine mammals: in- creasing impact of non-ortho and mono-ortho coplanar polychlorinated biphenyl from land to ocean. Arch. Environ. Contam. Toxicol. 18: 850-857 (1987). 13. Schmidt, L. J., and Hesselberg, R. J. A rapid analytical method for ahh- active PCB congeners. In: Proceedings of the 38th American Society for Mass Spectrometry Conference, Tucson, AZ, June 3-8, 1990. American Society for Mass Spectrometry, East Lansing, MI, 1990, pp. 1483-1484. 14. Tanabe, S., Kannan, N., Ono, M., and Tatsukawa, R. Toxic threat to marine mammals: increasing toxic potential of non-ortho and mono-ortho coplanar PCBS from land to ocean. Chemosphere 18: 485-490 (1989). 15. Asplund, L., Grafstrom, A.-K, Haglund, P., Jansson, B., Jernnas, U., Mace, D., Strandell, M., and de Wit, C. Analysis of non-ortho polychlorinated biphenyl and polychlorinated naphthalenes in Swedish diox- in survey samples. Chemosphere 20: 1481-1488 (1990). 16. Rappe, C., Bergqvist, P.-A., Bergek, S., Bostrom, M., Buser, H,-R., and Nygren, M. Levels of various PCDDs, PCDFs, planar PCB, and PCN in various fish oils. Presented at the Ninth International Symposium on Chlorinated Dioxins and Related Compounds, Dioxin '89, Toronto, Canada, September 17-22, 1989. 17. Koistinen, J., Paasivirta, J., and Vvorinen, P. J. Dioxins and other planar polychloroaromatic compounds in Baltic, Finnish, and Arctic fish samples. Chemosphere 19: 527-530 (1989). 18. Jarnberg, U., Haglund, P., Grafstrom, A. K., Asplund, L., Lexen, K., de Wit, C., Strandell, M., Jansson, B, Olsson, M., and Jonsson, B. Levels of non-ortho polychlorinated biphenyl and polychlorinated naphthalenes in fish and sediment samples. In: Organohalogen Compounds: Toxicology, Environment, Food, Exposure-Risk, Vol. I (O. Hutzinger and H. Fiedler, Eds.), Ecoinforma Press, Bayreuth, Germany, 1990, pp. 423-426. 19. Hong, C.-S., and Bush, B. Determinationof mono- and non-ortho coplanar PCBS in fish. Chemosphere 21: 173-181 (1990). 20. Abdel-Hamid, F. M., Moore, J. A., and Matthews, H. B. Comparative Study of 3,4,3 ',4-tetrachlorobiphenyl in male and female rats and female monkeys. J. Toxicol. Environ. Health 7: 181-191 (1981). 21. Mills, C. D., Mills, R. A., Sleight, S. D., and Aust, S. D. Toxicity of 3,4,5,3 4 5'-hexabrominated biphenyl and 3,3',4,4 -tetrabrominated biphenyl. lbxicol. Appl. Pharmacol.78: 88-95 (1985). 22. Phillips. D. L., Smith, A. B., Burse, V. W., Steele, G. K., Needham, L. L., and Hannon, W. H. Half-life of polychlorinated biphenyl in occupa- tionally exposed workers. Arch. Environ. Health. 44: 351-354 (1989). 23. Tanabe, S. A need for reevaluationofPCBtoxicity. Pllut. Bull. 20: 247-248 (1989). 24. Tanabe, S., Kannan, N., Subramanian, A., Wtanabe, S., Ono, M., and Tat- sukawa, R. Occurrence and distribution of toxic coplanar PCBs in the biota. Chemosphere 16: 1965-1970 (1987). 25. Kannan, N., Tanabe, S., and Tatsukawa, R. Potentially hazardous residues of non-ortho chlorine substituted coplanar PCBs in human adipose tissue. Arch. Environ. Health 43: 11-14 (1988). 26. Miyata, H., Takayama, K., Ogaki, J., Mimura, M., Kashimoto, T., and Yamada, T. Levels of PCDDs, coplanar PCBs and PCDFs in patients with Yusho disease and in the Yusho oil. Chemosphere 18: 407-416 (1989). 27. Kashimoto, T., Takayama, K., Mimura, M., Miyata, H., Murakami, Y., and Matsumoto, H. P., CDDs, PCDFs, PCBs, coplanar PCBs and organochlorinated pesticides in human adipose tissue in Japan. Chemosphere 19: 921-926 (1989). 28. Noren, K., and Lunden, A. Trend studies of polychlorinated biphenyl, dibenzo-p-dioxins and dibenzofurans in human milk. In: Organohalogen Compounds: Toxicology, Environment, Food, Exposure-Risk, Vol. 1 (O. Hutzinger and H. Fiedler, Eds.), Ecoinforma Press, Bayreuth, Germany, 1990, pp. 263-266. 29. Patterson, D. G., Jr., Lapeza, C. R., Jr., Barnhart, E. R., Groce, D. F., and Burse, V. W. Gas chromatographic/mass-spectrometric analysis of human serum for non-ortho (coplanar) and ortho substituted PCBs using isotope- dilution mass spectrometry. Chemosphere 19: 127-134 (1989). 30. Patterson, D. G., Jr., Todd, G. D., Turner, W. E., Isaacs, S. G., and Needham, L. L. Levels of non-ortho-substituted polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans in human serum and adipose tissue, In: Organohalogen Compounds, Vol, 4. Miscellaneous Papers and Index (O. Hutzinger and H. Fiedler, Eds.), Ecoinforma Press, Bayreuth, Germany, 1990, pp. 133-136. 31. Beck, H., Dross, A., and Mathar W. 3,3'4,4'-Tetrachlorobiphenyl in human fat and milk samples. Chemosphere 19: 1805-1810 (1989). 32. Patterson D. G., Jr., Holler, J. S., Lapeza, C. R., Jr., Alexander, L. R., Groce, D. F., O'Connor, R. C., Smith, S. J., Liddle, J. A., and Needham, L. L. High-resolution gas chromatographic/high-resolution mass spec- troscopic analysis of human adipose tissue for 2,3,7,8-tetrachlorodibenzo- p-dioxin. Anal. Chem. 58: 705-713 (1986). 33. Lapeza, C. R., Jr., Patterson, D. G. Jr., and Liddle, J. A. An automated ap- paratus for the extraction and enrichment of 2,3,7,8-TCDD in human adipose. Anal. Chem. 58: 713-716 (1986). 34. Patterson, D. G, Jr., Hampton, L., Lapeza, C. R., Belser, W. T., Green, V., Alexander, L., Needham, L. L. High-resolution gas chromatographic/ high-resolution mass spectrometric analysis of human serum on a whole- weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Anal. Chem. 59: 2000-2005 (1987). 35. Patterson, D. G., Jr., Furst, P., Henderson, L. O., Isaacs, S. G., Alexander, L. R., Turner, W. E., Needham, L. L., and Hannon, H. Partitioning of in- vivo bound PCDDs/PCDFs among various compartments in whole blood. Chemosphere 19: 135-142 (1989). 36. Patterson, D. G., Jr., Holler, J. S., Belser, W. T., Boozer, E. L., Lapeza, C. R., and Needham, L. L. Determination of 2,3,7,8-TCDD in human adipose tissue on whole weight and lipid bases. Chemosphere 16: 935-936 (1987). 37. Akins, J. R., Waldrep, K., and Bernert, J. T., Jr. The estimation of total serum lipids by a completely enzymatic 'summation' method. Clin. Chem. Acta 184: 219-226 (1989). 38. Smith, L. M., Stalling, D. L., and Johnson, J. L. Determination of part- per-trillion levels of polychlorinated dibenzofurans and dioxins in en- vironmental samples. Anal. Chem. 56: 1830-1842 (1984). 39. Turner, W. E., Issacs, S. G., Patterson, D. G., Jr., and Needham, L. L. En- vironmental carcinogens - methods of analysis and exposure measurement, Vol. 11. Polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (C. Rappe and H. R. Buser, Eds), International Agency for Research on Cancer, Lyon, France, 1991, pp. 343-355. 40. Patterson, D. G. Jr., Fingerhut, M. A., Roberts, D. R, Needham, L. L., Haring-Sweeney, M., Marlow, D. A., Andrews, J. S., andHalperin, W. E. Levels of polychlorinated dibenzo-p-dioxins (PCDDS) and dibenzofurans (PCDFs) in workers exposed to 2,3,7,8-TCDD. Am. J. Ind. Med. 16: 135-146 (1989). 41. Thornburg, K. R., Boggess, K. E., and Stanley, J. S. Thedeterminationof coplanar PCBs, PCDDs, and PCDFs in mothers milk by high resolution gas chomatgraphy/high resolution mass spectrometry. In: Proceedings of the 39th American Society of Mass Spectrometiy Conference, Nashville, TN, May 19-24, 1991, American Society for Mass Spectrometry, East Lansing, MI, 1991, p. 99. 204 PA77ERSONETAL. 42. Georgii, S., and Brunn, H. Polychlorinated biphenyl (PCB) in human fat tissue. In: Organohalogen Compounds; Vol. 1. Toxicology, Environment, Food, Exposure-risk (O. Hutzinger and H. Fiedler, Eds.), Ecoinforma Press, Bayreuth, Germany, 1990, pp. 235-237. 43. Dewailly, E., Flaugnatti, R., Haguenoer, J. M., and Hemon, D. National study of polychlorinated biphenyl (PCBs) residues in human plasma, France: geographic and demographic factors (abstract TLS16). Presented at the Ninth International Symposium on Chlorinated Dioxins and Related Compounds, Dioxin '89, Toronto, Canada, September 21, 1989. 44. Mori, Y., Kikauta, M., Okinaga, E., and Okura, T. Levels of PCBs and organochlorine pesticides in human adipose tissue collected in Ehime prefecture. Bull. Environ. Contam. Toxicol. 30: 74-79 (1983). 45. Mes, J., Davies, D. J., Turton, D. Polychlorinated biphenyl and other chlorinated hydrocarbon residues in adipose tissue of Canadians. Bull. En- viron. Contain. Toxicol. 28: 97-104 (1982). 46. Robinson, P E., Mack, G. A., Remmers, J., Levy, R., and Mohadjer, L. Trends of PCB, hexachlorobenzene, and b-benzene hexachloride levels in the adipose tissue of the U.S. population. Environ. Res. 53: 175-192(1990). 47. NATO. International Toxicology Equivalency Factor Method of Risk Assess- ment for Complex Mixtures of Dioxins and Related Compounds. Report No. 176, North Atlantic Treaty Organization, Committee on the Challenges of Modern Society, 198& 48. Patterson, D. G., Jr., Ross, W., Turner, W. E., Alexander, L. R., Pirkle, J. L., Needham, L., and Liddle, J. A. Assessing human exposure to polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs): factors associated with a body burden measurement. Environ. Health Perspect. 49. Stanley, J. S., Ayling, R. E., Cramer, P. H., Thornburg, K. R., Remmers, J. C., Breen, J. J. Schwemberger, J., Kang, H. K., and Wtanabe, K. Polychlorinated dibenzo-p-dioxins and dibenzofuran concentration levels in human adipose tissue samples from the continental United States collected from 1971 through 1987. Chemosphere 20: 895-901 (1990). 50. Ersboell, A., Nygren, M., and Yrjanheikki, WHO-coordinated in- terlaboratory quality control studies on levels of PCBs, PCDDs, and PCDFs in human milk and blood. In: Organohalogen Compounds: Vol. 4. Miscellaneous Papers and Index (Q. Hutzingerand H, Fiedler, Eds.), Ecoin- forma Press, Bayreuth, Germany, 1990, pp. 169-174. 51. Luotamo, M., Jarvisalo, J., and Aitio, A. Assessment of exposure to polychlorinated biphenyls: analysis of selected isomers in blood and adipose tissue. Environ. Res. 54: 121-134 (1991). 52. Klasson, W. E., Jansson, J., Bergman, A., Brandt, I., Darneryd, P. O., 3,3'4,4'-Tetrachlorobiphenyl and 3,3',4,4',5-pentachlorobiphenyl tissue localization and metabolic fate in the mouse. Chemosphere 19: 809-812 (1989). 53. Sonzogni, W., Maack, L., Gibson, T., Degenhardt, D., Anderson, H., and Fiore, B. Polychlorinated biphenyl congeners in blood of Wisconsin sport fish consumers. Arch. Environ. Contam. Toxicol. 20: 56-60 (1991). 54. Duebelbeis, D. O., Pieczonka, G., Kapila, S., Clenenger, T. E., Yanders, A. F., and Wilson, J. D. Application of a dual column reaction chromatography system for confirmatory analysis of polychlorinated biphenyl congeners. Chemosphere 19: 143-148 (1989). 55. Luotamo, M. Assessment of Exposure to Polychlorinated Biphenyls. Dissertation, University of Helsinki, Helsinki, Finland, 1991. 56. Weber, J.-P. PCBs in Human Blood Plasma: Interlaboratory Comparison Program. Report for Round No. 4, Quebec Toxicology Center, Le Centre Hospitalier de I'Universite Laval-2705, 1991. 57. Fiore, B. J., Anderson, H. A., Hanranhan, L. P., Olson, L. J., and Son- zogni, W. C. Sport fish consumption and body burden levels of chlorinated hydrocarbons: a study of Wisconsin anglers. Arch. Environ. Health 44: 82-88 (1989). 58. Humphrey, H. E. B. Population studies of PCBs in Michigan residents. In: PCBs: Human and Environmental Hazards, Ann Arbor Science Publica- tions, Ann Arbor, MI, 1983, pp. 299-310. 59. Dewailly, E., Tremblay-Rousseau, H., Carrier, G., Groulx, S., Gingrass, S., Boggess, K., Stanley, J., and Weber, J. P. PCDFs, and PCBs in human milk of women exposed to a PCB fire and of women from the general population of the province of Quebec-Canada. In: Organohalogen Com- pounds, Vol. 1 Toxicology, Environment, Food, Exposure-Risk (O. Hut- zinger and H. Fiedler, Eds.), Ecoinforma Press, Bayreuth, Germany, 1990, pp. 227-230. 60. Toxic Substances Control Act (TSCA), U.S., Environmental Protection Agency, 15 United States Code 2605e. 61. Horwitz, W., Ed. Official methods of Analysis of the Association of Of- ficial Analytical Chemists, 13th ed., Association of Official Analytical Chemists, Washington, DC, 1980, p.472. 62. Burse, V. W., Groce, D. F., Korver, M. P., McClure, P. C., Head, S. L., Needham, L. L., Lapeza, C. R. Jr., and Smrek, A. L. Use of reference pools to compare the qualitative and quantitative determination of polychlorinated biphenyls by packed and capillary gas chromatography with electron cap- ture detection, Part 1. Serum. Analyst 115: 243-251 (1990).