In vitro reproductive toxicity of polychlorinated biphenyl congeners 153 and 126

Abstract<195>This study was conducted to investigate the applicability of an in vitro technique for maturation, fertilization, cleavage, and growth to blastocysts of bovine oocytes to investigate reproductive toxicologic effects. During maturation, the oocytes were exposed to the di-ortho-substituted PCB congener 2,2′,4,4′,5,5′-CB (PCB 153) in the three concentrations 0.84 ng/mL, 8.4 ng/mL, and 84 ng/mL or to the non-ortho-substituted PCB congener 3,3′4,4′,5-CB (PCB 126) in the three concentrations 1.006 pg/mL, 10.06 pg/mL, and 100.6 pg/mL and compared with control groups. PCB 153 had no effect on maturation but resulted in a reduced proportion of oocytes that cleaved at the highest concentration. There were no differences in blastocyst development among groups. PCB 126 resulted in a reduction in maturation percentage at the highest concentration and in blastocyst development at all concentrations. These results demonstrated adverse effects of PCB congeners on bovine oocytes and showed that this system can be used to evaluate toxic effects on oocytes and preimplantation-stage embryos.     

Distribution and elimination in vivo of polychlorinated biphenyl (PCB) isomers and congeners in the pigeon

1. Pigeons were injected with a single dose of commercial PCB mixtures (Aroclor 1248 plus Aroclor 1260), killed 120 h later and the abundance of individual PCBs was determined in adipose tissue, gonads, liver, brain, kidney, heart, muscle and blood. 2. Elimination factors for individual PCBs were calculated. Values of greater than 1 were obtained for PCBs with meta-para-unsubstituted carbon atoms in at least one ring, indicating that elimination exceeded accumulation in all or most tissues. By contrast, ortho-meta unsubstituted PCBs had elimination factors less than 1, thus indicating their impaired removal. 3. Tissues with high microsomal monooxygenase activity had the highest elimination factors for individual PCBs (i.e. liver greater than kidney greater than muscle greater than heart). 4. Distribution of individual PCBs was independent of sex and of ortho-chlorine substitution and showed that 90% of total PCBs in cadavers was present in adipose tissue, 2% in kidneys, 1% each in brain, muscle and heart and less than 0.1% in blood. 5. The distribution of the highly toxic non-ortho and mono-ortho substituted PCBs did not differ amongst all tissues analysed. 6. The present studies indicate that elimination of PCBs in vivo is favoured by the molecular feature of unsubstituted meta-para carbon atoms in the biphenyl moiety.     

Distribution and elimination in vivo of polychlorinated biphenyl (PCB) isomers and congeners in the pigeon

1. Pigeons were injected with a single dose of commerical PCB mixtures (Aroclor 1248 plus Aroclor 1260), killed 120 h later and the abundance of individual PCBs was determined in adipose tissue, gonads, liver, brain, kidney, heart, muscle and blood.

2. Elimination factors for individual PCBs were calculated. Values of >1 were obtained for PCBs with meta-para-unsubstituted carbon atoms in at least one ring, indicating that elimination exceeded accumulation in all or most tissues. By contrast, ortho-meta unsubstituted PCBs had elimination factors <1, thus indicating their impaired removal.

3. Tissues with high microsomal monooxygenase activity had the highest elimination factors for individual PCBs (i.e. liver> kidney > muscle > heart).

4. Distribution of individual PCBs was independent of sex and of ortho-chlorine substitution and showed that 90% of total PCBs in cadavers was present in adipose tissue, 2% in kidneys, 1% each in brain, muscle and heart and <0.1% in blood.

5. The distribution of the highly toxic non-ortho and mono-ortho substituted PCBs did not differ amongst all tissues analysed.

6. The present studies indicate that elimination of PCBs in vivo is favoured by the molecular feature of unsubstituted meta-para carbon atoms in the biphenyl moiety.     

Effects of non-dioxin-like polychlorinated biphenyl congeners (PCB 101, PCB 153 and PCB 180) alone or mixed on J774A.1 macrophage cell line: modification of apoptotic pathway

Non-dioxin-like polychlorinated biphenyls (PCBs) are stable and lipophilic chemicals that persist in the environment and tend to bioaccumulate in the food chains. In the present study, we have investigated the effect of PCBs 101, 153, and 180 on macrophage J774A.1 by assessing cell viability and apoptotic cell death. We have combined morphological techniques and biochemical ones to establish the relevance of apoptosis in macrophage cell death induced by PCBs, alone or in combination. Treatment with the examined PCBs caused the loss of cell viability and accelerated apoptosis in a concentration-dependent manner. Moreover, a synergistic effect on cell death and apoptosis was evidenced for all PCBs at concentrations which were inactive alone. The apoptosis induced by PCBs involved the increase of caspase-3 activity. Also, Bcl-2 and Bax proteins were assessed to elucidate the apoptosis machinery induced in macrophage cultures by PCBs. Our results indicate that the increase in PCB-induced apoptosis correlates with a reduction in the expression of antiapoptotic Bcl-2 and an increase in the expression of proapoptotic Bax. Interestingly, concentrations of PCBs inactive by themselves induce apoptosis when PCBs are combined. In conclusion, our findings suggest that, although less toxic than dioxin like congeners, the examined non-dioxin-like PCBs are equally dangerous as immunotoxic pollutants, also considering their presence as mixtures at higher levels than dioxin-like PCBs in biotic and abiotic matrices.     

Dopamine-dependent behavior in adult rats after perinatal exposure to purity-controlled polychlorinated biphenyl congeners (PCB52 and PCB180)

Since knowledge about toxic effects of non-dioxinlike (NDL) PCBs is fragmentary, regulatory panels have concluded that risk assessment of these congeners is hampered or impossible. As the dopaminergic system is one of the main targets in PCB-related neurotoxic effects after developmental exposure, we selected catalepsy induced by the dopamine receptor blocker haloperidol to characterize effects of the NDL congeners PCB52 and PCB180 in adult offspring from exposed rat dams. Rat dams were treated with PCB congeners by gavage using six dose levels (total doses: PCB52 – 0, 30, 100, 300, 1000 or 3000 mg/kg body wt.; PCB180 – 0, 10, 30, 100, 300, or 1000 mg/kg body wt.) to allow benchmark dose analysis of the results. Testing of adult offspring (starting at 180 days of age) for catalepsy induced by injection with haloperidol revealed slightly prolonged latencies to movement onset in female offspring exposed to PCB52. Exposure to PCB180 resulted in more pronounced effects, with generally reduced latencies in male offspring. These results indicate reduced dopaminergic activity after PCB52 exposure, whereas the outcome for PCB180 may be related to increased extracellular dopamine as reported in the literature. Benchmark dose analyses revealed that both PCB congeners exerted effects mainly at moderate exposure levels. Together, these results underline the importance of effects on the dopaminergic system as indicated by studies in human females after occupational PCB exposure.     

Ortho-substituted polychlorinated biphenyl (PCB) congeners (95 or 101) decrease pituitary response to thyrotropin releasing hormone

Polychlorinated biphenyl compounds (PCBs) are global environmental contaminants that cause disruption of the endocrine system in humans and wildlife. Recently, we reported that acute exposures to ortho-PCB congeners 95 (2,3,6-2',5') or 101 (2,4,5,-2',5') causes changes in the performance of the hypothalamo-pituitary-thyroid (HPT)-axis in developing rats through mechanism(s) not yet clear. The functionality of the HPT-axis was evaluated by using the thyrotropin releasing hormone (TRH) test following acute exposure to PCBs 95 or 101. Weanling female rats received PCBs 95 or 101 intraperitoneally (ip) at 32 mg/kg for 2 consecutive days and synthetic TRH was given 48 h after the last dose. Serum thyroxine (T4) levels decreased following exposure to both the congeners. In PCB 95-treated rats, serum thyroid stimulating hormone (TSH) levels were elevated in response to TRH, but were only 40% of the control response to TRH. No significant changes were seen in serum prolactin (PRL), hypothalamic dopamine (DA), thyroid gland morphology, or epithelial cell proliferation. It is suggested that these congeners, interfere with the HPT-axis by causing a subnormal response of the pituitary and thyroid to TRH stimulation.     

Meta-analysis of microarray datasets for the risk assessment of coplanar polychlorinated biphenyl 77 (PCB77) on human health

Polychlorinated biphenyls (PCBs) are persistent organic compounds that have been banned since 1970s, but continue to contaminate the environment. PCBs are categorized into two structural groups: coplanar and non-coplanar PCBs. The coplanar PCBs are dioxin-like potent toxic compounds. To evaluate their effects on humans, we chose a coplanar PCB77 for data analysis. We performed meta- analysis by integrating datasets via the Rank Product method, and identified 375 up- and 66 down- regulated differentially expressed genes (DEGs). Notably, up-regulated genes were significantly associated with liver and kidney diseases. Using gene ontology enrichment, we found that the up-regulated DEGs were significantly enriched in the apoptotic process (false discovery rate, FDR=1.62e-10) and response to unfolded protein (FDR=7.65e-10). Protein-protein interaction networks identified the hub proteins containing HSP90AB1 and HSPA5. These findings suggest that our DEGs may provide a robust set of genetic markers for PCB77.     

Pathology of chronic polychlorinated biphenyl (PCB) feeding in rats

The hepatocarcinogenic effect of Clophen A 30 and Clophen A 60 was tested in male weanling rats by long-term feeding over a period of 832 days. The mortality rate was investigated in 100-day intervals. In the first 800 days liver carcinoma accounted for 21% of necropsies in the Clophen A 60 group but only 2% of the necropsies in the Clophen A 30 group and none in the control animals. The tumors were first observed after 700 days. After 800 days hepatocellular carcinoma was the most common lesion observed in the Clophen A 60 animals (61%) whereas it was only observed in 3% of animals in the Clophen A 30 group and 2% in the controls. Preneoplastic lesions, such as foci of hepatocellular alterations and neoplastic nodules, were first observed after Day 500. The incidence of foci predominated in all time intervals, but an increase in neoplastic nodules and hepatocellular carcinomas was observed with increased time. There was a marked trend from foci to neoplastic nodule to hepatocellular carcinoma with time. The total mortality rate and the incidence of thymoma, inflammatory lesions of the urogenital tract, in the experiment were significantly reduced by Clophen administration. Whether this protective effect could be induced by polychlorinated biphenyls (PCBs) is discussed.     

Lack of effects of some individual polybrominated diphenyl ether (PBDE) and polychlorinated biphenyl (PCB) congeners on human lymphocyte functions in vitro

The structural similarities between polybrominated diphenyl ethers and immunotoxic halogenated aromatic compounds suggest that the polybrominated diphenyl ethers might affect the immune system. The present study was undertaken to investigate the immunological effects of some purified PBDE-congeners on human lymphocyte function in vitro. Polychlorinated biphenyl congeners were also included in the study. Mitogen-induced DNA synthesis and immunoglobulin synthesis by lymphocytes from blood donors were examined following polybrominated diphenyl ether or polychlorinated biphenyl exposure in vitro in order to determine the immunotoxic potential of these substances. No effects on mitogen-induced proliferation or immunoglobulin synthesis were observed after exposure of cells to concentrations up to 10⁻⁵ M. The negative findings in this study indicate that certain functions of human peripheral lymphocytes, i.e. proliferation and immunoglobulin synthesis, are insensitive to the direct action of polybrominated diphenyl ethers and polychlorinated biphenyls. Our results are in accordance with other recent studies in which no effects on immunological parameters were demonstrated by exposure of lymphocytes to polyhalogenated aromatic hydrocarbons in vitro.     

Scale-dependence in polychlorinated biphenyl (PCB) exposure effects on waterbird habitat occupancy

Spatial scale is rarely considered in population-level assessments of contaminant impacts on wild animals; as a result misinterpretation of the relationship between contaminant exposure and population status may occur. We assessed the strength of expression of polychlorinated biphenyl (PCB) exposure effects at local vs. regional spatial scales on population status in five species of waterbirds, “bioaccumulators” often promoted as indicators of contaminant effects in aquatic ecosystems. Our focus was the upper Hudson River where PCBs occur at levels reported to have adverse impacts on wild birds. At the local scale, waterbird habitat occupancy was estimated from 220 repeat surveys made between 2001 and 2010 along the same survey route divided into 25 contiguous river segments with markedly different PCB concentrations. At the regional scale, waterbird habitat occupancy in relation to proximity to the upper Hudson River was estimated across 1248 Breeding Bird Atlas survey blocks while controlling for region-wide variation in habitat availability. At the local scale, many associations of habitat and sampling covariates with species detection probabilities were evident but none, including PCB concentration, with habitat occupancy, extinction or colonization of a given river segment. At the regional scale, survey effort and habitat factors not related to PCB exposure were the most important drivers of waterbird occurrence although two species were more likely to occur farther from the contaminated river segment. Spatial scale clearly mediates expression of contaminant impacts on wild bird populations; large-scale, expert-generated databases provide an underused opportunity for better delineating the spatial scales at which population impacts occur and risk assessments should be performed.     

Effects of gestational and lactational exposure to coplanar polychlorinated biphenyl (PCB) congeners or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid hormone concentrations in weanling rats

Perinatal exposure to polychlorinated biphenyl (PCB) mixtures or to certain ortho-substituted PCB congeners dramatically reduces circulating thyroxine (T4) concentrations. It is not clear whether perinatal exposure to coplanar PCBs or2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a similar effect. In this study, time-mated Sprague-Dawley rats were dosed with 2 or 8 mg/kg/day PCB 77 (3,3′,4,4′-tetrachlorobiphenyl), 0.25 or 1.00 μ/kg/day PCB 126 (3,3′,4,4′,5-pentachlorobiphenyl), 0.025 or 0.10 μg/kg/day TCDD, or corn oil vehicle orally on gestation days 10–16. At weaning, plasma total T4 concentrations in PCB 77 and TCDD high-dose female pups were significantly depressed, but the changes were modest (84.4 and 79.6% of control, respectively). T4 concentrations in PCB 126 high-dose females and all high-dose males were also depressed slightly, but the changes were not statistically significant. UDP-Glucuronosyl transferase (UDP-GT) activity towards 4-nitrophenol was increased in all high-dose groups. Thus, the modest decreases in T4 could be due in part to increased T4 glucuronidation by UDP-GT. Triiodothyronine (T3) and thyroid stimulating hormone (TSH) concentrations were unchanged in all groups. In contrast to the minor changes in thyroid hormone status, liver microsomal ethoxyresorufin-O-deethylase (EROD) was markedly induced in all exposure groups and thymus weights were depressed in the high-dose groups. Because doses of coplanar PCBs or TCDD that caused marked induction of EROD activity had only minor effects on T4, we conclude that changes in thyroid hormone status at weaning are not among the more sensitive effects of perinatal exposure to these compounds.     

Genotoxic effects of polychlorinated biphenyls (PCB 153, 138, 101, 118) in a fish cell line (RTG-2)

Polychlorinated biphenyls (PCBs) are persistent pollutants in aquatic environments, often causing the decline or disappearance of wild populations. The primary aim of this study was to investigate the genotoxic effects of some PCBs (PCB153 (2,2′,4,4′,5,5′-hexachlorobiphenyl) and 138 (2,2′,3,4,4′,5′-hexachloro-biphenyl), both non-dioxin-like compounds, and the pentachlorobiphenyls PCB118 (2,3′,4,4′,5-) and 101 (2,2′,4′,5,5′-), the former an ortho-substituted, low-affinity dioxin-like compound and the latter a non-coplanar congener classified as non-dioxin-like) in fish cells (RTG-2). These congeners are mostly present in surface waters and in edible aquatic organisms and the loss of DNA integrity in vitro serves as a sensitive biomarker of cytogenetic alterations and is considered as an initial step for the identification of genotoxic effects.The alkaline comet assay and the micronucleus test show clear genotoxic damage after short and longer exposure (2 and 24 h) to maximum soluble, non-cytotoxic doses, evident sooner with PCBs 101 and 118. Oxidative stress situations involving ROS release, reduction in total GSH, lipid peroxidation and alteration to superoxide dismutase, seen after exposure with all the congeners, though with different kinetics, seem the most likely explanation for the genotoxic damage. This appears to be confirmed by the modified comet assay (pH 10) for detection of oxidized bases using endonuclease III. The increased generation of intracellular ROS might explain the apoptosis seen after treatment with the single PCBs and evaluated on the basis of the rise in 3-7 caspase activity. Therefore both the non-coplanar, non-dioxin-like PCBs (153, 138, 101) and the low-affinity dioxin-like compound PCB118 cause evident genotoxic damage, probably as a consequence of oxidative stress.     

Establishment of the cumulative margin of exposure for a group of polychlorinated biphenyl (PCB) congeners using an improved approach that accounts for both variability and uncertainty

In this study, the cumulative margin of exposure (MOE) was estimated for a group of polychlorinated biphenyls (PCBs) based on reduction of hepatic retinoids as a mode-of-action relevant toxicological endpoint. The MOE was defined as the ratio between a reference dose, derived using the benchmark dose (BMD) approach, and the estimated human dietary PCB exposure. A distribution for the cumulative MOE was established, taking into account inter- and intra-individual variability as well as uncertainty in data measurements. The cumulative MOE reflected mainly the MOE for PCB 126; other PCB congeners had little contribution to the cumulative exposure and MOE. The median of the 0.1st percentile for the cumulative MOE was about 20 for women; depending on the percentile, cumulative MOE was 2–4 times higher for men compared to women. Furthermore, a relative potency factor (RPF) based approach was compared to an RPF-free approach for estimating the cumulative MOE. The RPF-free approach more completely accounts for variability and uncertainty but is more data intensive than the RPF-based approach, which can be more easily implemented in practice and allows for a use of historical data on RPFs. Consideration of the discussed approaches may contribute to improving cumulative health risk assessments.     

Immunotoxic potencies of polychlorinated biphenyl (PCB), dibenzofuran (PCDF) and dibenzo-p-dioxin (PCDD) congeners in C57BL/6 and DBA/2 mice

The dose-dependent effects of a single acute exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 1,2,3,7,9-PeCDF, 1,3,6,8-tetrachlorodibenzofuran (TCDF), 3,3′,4,4′,5-pentachlorobiphenyl (pentaCB), and 3,3′,4,4′,5,5′-hexaCB on the suppression of the splenic plaque-forming cell (PFC) response to the T-cell-independent antigen trinitrophenyl-lipopolysaccharide were determined in C57BL/6 and DBA/2 mice. In addition, the induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity was also measured in these animals. 2,3,7,8-TCDD and 2,3,4,7,8-PeCDF were the most immunotoxic congeners in both strains of mice and with the exception of the latter congener, the ED₅₀ values for each compound were lower in the C57BL/6 than the DBA/2 mice. 2,3,7,8-TCDD induced hepatic microsomal EROD activity in both strains of mice whereas the other congeners were considerably less active or inactive as inducers. The results of this study demonstrated that for the halogenated aromatic hydrocarbons the immunotoxic response was a more sensitive indicator of exposure than the induction of CYP1A1 activity. The rank order for the immunotoxic potencies of the chlorinated aromatic compounds used in this study was 2,3,7,8-TCDD ≈ 2,3,4,7,8-PeCDF > 3,3′,4,4′,5-pentaCB ≈ 3,3′,4,4′,5,5′-hexaCB > 1,2,3,7,9-PeCDF > 1,3,6,8-TCDF. The order of activity for these congeners was similar for other Ah receptor-mediated responses and these results coupled with the differential responsiveness of the C57BL/6 and DBA/2 mice confirms the role of aryl hydrocarbon (Ah) receptor in mediating the suppression of this T-cell-independent response.     

Effects of ortho- and non-ortho-substituted polychlorinated biphenyl congeners on the hepatic monooxygenase system in scup (Stenotomus chrysops)

Polychlorinated biphenyl congeners that are abundant in environmental samples, and known to induce hepatic monooxygenase isozymes in the P450IA gene subfamily in mammals, were examined for their ability to induce hepatic monooxygenase activity in scup, a marine teleost. Scup were dosed ip with 3,3',4,4'-tetrachlorobiphenyl (congener 77), 2,3,3',4,4'-pentachlorobiphenyl (congener 105), 2,3',4,4',5-pentachlorobiphenyl (congener 118), 2,2',3,4,4',5'-hexachlorobiphenyl (congener 138), 2,2',3,3',4,4'-hexachlorobiphenyl (congener 128), or beta-naphthoflavone and examined for increases in ethoxyresorufin O-deethylase (EROD) activity, immunodetectable cytochrome P450E (the EROD catalyst in scup), and in vitro translatable mRNA for P450E. Monooxygenase parameters were significantly induced only by 3,3',4,4'-tetrachlorobiphenyl (TCB). However, while translatable mRNA for P450E was induced at all doses (1, 5, and 10 mg/kg), EROD activity and P450E were decreased at the 5 and 10 mg/kg doses, relative to the response at 1 mg/kg. A strong relationship between residual TCB concentration in the liver and the decreased EROD activity was evident at the higher doses of TCB. Aminopyrine N-demethylase, a monooxygenase activity not catalyzed by P450E, was unaffected by TCB treatment, indicating a specificity in the TCB effect. Analysis in vitro revealed that TCB was a potent competitive inhibitor of EROD activity, with half-maximal inhibition at 0.3 microM, near the Km for ethoxyresorufin, suggesting one mechanism for the in vivo effect of TCB. These results demonstrate that PCB congeners with ortho-chlorine substitution, and which are effective inducers of AHH and EROD activity in mammals, are ineffective, at the doses tested, as inducers in the teleost scup.     

Comparison of polychlorinated biphenyl (PCB) induced effects on innate immune functions in harbour and grey seals

Polychlorinated biphenyls (PCBs) are known to have detrimental effects on the innate immune system of several mammalian species. Top predators such as marine mammals may be badly affected as PCBs can bioaccumulate in their blubber to high concentrations and previous studies have suggested that harbour seals may be particularly vulnerable to the immunotoxic effects of such contaminants. To investigate the effects of PCBs on innate immune functions in phocid seals, blood samples were collected from harbour and grey seals and exposed in vitro to a mixture of Aroclors. Separated mononuclear (PBMCs) and polymorphonuclear (PMNCs) leukocytes from each species were incubated with Aroclors (at 3 and 30 ngml(-1)) for 3 and 24 h incubation periods, after which phagocytosis, respiratory burst and cytotoxic activity were measured. The phagocytic activity of harbour seal PMNCs was decreased at both incubation times and at both Aroclor concentrations tested, but there was no effect on the grey seals. Similarly, the respiratory burst activity of harbour seals was decreased at both incubation times, but only at the higher concentration used. There were no differences in the cytotoxic activity of the PBMCs with respect to incubation times or concentrations in either species. However, differences were observed in the level of cytotoxic activity against YAC-1 target cells, with the grey seal PBMCs showing higher levels of activity. The observed differences in phagocytosis, respiratory burst and cytotoxic activity of the leukocytes following incubation with PCBs may have implications for the previously recorded differences in disease susceptibility between grey and harbour seals.     

Metabolism-related spectral characterization and subcellular distribution of polychlorinated biphenyl congeners in isolated rat hepatocytes

The disposition and biotransformation of 4,4'-dichlorobiphenyl (4-DCB), 2,2',3,3',6,6'-hexachlorobiphenyl (236-HCB), and 2,2',4,4',5,5'-hexachlorobiphenyl (245-HCB) were studied in isolated rat hepatocyte suspensions. The polychlorinated biphenyls (PCBs) were taken up rapidly by the cells but incompletely metabolized. Metabolism followed first-order Michaelis-Menten kinetics for 20 min and plateaued by 60 min, at which point only 32% of 4-DCB (0.005 to 100 microM) and 60% of 236-HCB (0.001 to 100 microM) were metabolized, while metabolism of 245-HCB was not detected (0.1 to 200 microM). Kinetic studies revealed that both 4-DCB and 236-HCB were metabolized by two Michaelis-Menten processes, displaying high- and low-affinity binding. Readdition of congener once metabolism plateaued resulted in a reinitiation of metabolism with the same proportion of metabolites produced. The termination of metabolism was not due to destruction of the mixed-function oxidases or to depletion of cofactors. The metabolism of PCB congeners is influenced by the affinity of the congener for cytochrome P-450 and partitioning of the congener within the hepatocyte. Analysis of absorbance differences (delta absorbance 390-240 nm) of equimolar concentrations of congener (100 microM) revealed that 236-HCB displayed the greatest affinity of binding to cytochrome P-450 followed by 4-DCB, while 245-HCB showed virtually no binding. Microsomal preparations demonstrated equivalent but greater absorbance values. Subcellular distribution of 14C-labeled congener and its metabolites showed that the majority of radioactivity appeared in the cytosolic fraction, representing 70% of the dose added for each congener. Cytosolic binding of congener and metabolites may influence both the availability of congener to cytochrome P-450 and the excretion rate of metabolites from the cell.     

Concentrations and frequencies of polychlorinated biphenyl congeners in a Native American population that consumes Great Lakes fish

OBJECTIVE: Polychlorinated biphenyl congener profiles were examined in serum samples from 61 Native American (Ojibwa) volunteers who regularly consumed fish harvested from the Great Lakes region. A total of 93 peaks are reported which represent 126 individual chlorobiphenyls. RESULTS: When ranked by frequency, 13 peaks comprising single or co-eluting chlorobiphenyls occurred in all 61 samples (a frequency of 100%). These included chlorobiphenyls 138 + 158 + 163, 105 + 132 + 153, 180, 118, 196 + 203, 74, 182 + 187, 199, 183, 114 + 134, 195 + 208, 206, and 194. These 13 peaks also occurred at concentrations higher than those of all other measured chlorobiphenyls, except for the addition of the peak containing chlorobiphenyls 170 and 190, which was below detection in 15% of the samples and ranked fifth in average concentration. The highly chlorinated chlorobiphenyls resembled human serum profiles previously reported in the literature. METHODS: Individual chlorobiphenyls were identified using a gas chromatograph equipped with a 60-meter DB-5 capillary column and electron capture detection. CONCLUSION: When compared to other human residue analyses for fish-eating populations, the Ojibwa samples contained higher proportions of lightly chlorinated and labile chlorobiphenyls such as 8, 16 + 32, 17, 18, 25, 41 + 64 + 71, 33, 52, 110, and 129. These proportions were similar to those found in carp, whitefish, or whitefish livers harvested from the Great Lakes region. These data indicate that regular meals of lower trophic level fish, such as whitefish from the Great Lakes, may distort steady-state human chlorobiphenyl profiles with respect to certain lightly chlorinated or labile chlorobiphenyls.