Potency of mixtures of polychlorinated biphenyls as inducers of dioxin receptor-regulated CYP1A activity in rat hepatocytes and H4IIE cells

Among the polychlorinated biphenyls (PCBs), a family of widespread environmental pollutants, the most toxic non-ortho-substituted coplanar (non-ortho coplanar) congeners are thought to act as strong dioxin (aryl hydrocarbon) receptor agonists leading to adverse effects, such as body weight loss, immunosuppression, thymic atrophy, hepatotoxicity, tumor promotion, and disturbances of steroid hormone action. Since PCBs are present in environmental and tissue samples as complex mixtures, we investigated the possible interaction of non-ortho coplanar congeners with other major PCBs, which are less active or inactive as dioxin receptor agonists. As a parameter for dioxin receptor activation, induction of CYP1A-catalyzed 7-ethoxyresorufin O-deethylase (EROD) was determined in rat hepatocytes in primary culture and in the rat hepatoma cell line H4IIE. In rat hepatocytes, individual EC50-values and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalency factors (TEFs) for the non-ortho and mono-ortho coplanar PCBs 126, 169, 105, 118 and 156, were in good agreement with published data from in vivo experiments, while in H4IIE cells coincidence was lower. However, in both cell systems TEFs for PCB 77 were significantly higher than reported from experiments in rats. In an approximately equipotent mixture the six potent PCB congeners showed perfect additive behaviour in both cell systems. In contrast, addition of a tenfold surplus of abundant mono- and di-ortho PCBs (28, 52, 101, 138, 153 and 180) led to an almost threefold higher TEF than predicted. This finding suggests a moderate synergistic enhancement of the inducing potency of potent PCBs by less potent congeners, present in abundance in environmental and tissue samples.     

Interactions between 2,3,7,8-TCDD and PCBs as tumor promoters: limitations of TEFs

The assessment of the carcinogenic risk of polychlorinated dioxins (PCDDs), furans (PCDFs), and biphenyls (PCBs) by TEFs is hampered by species- and tissue-specific responses that cannot readily be explained by differences in the Ah receptor levels but may be due to events subsequent to ligand binding to the Ah receptor. Moreover, PCDDs and related compounds accumulate in the environment, in animal and human tissues as highly complex mixtures. Thus, comprehensive risk assessment should include all Ah receptor ligands and agents that modulate the Ah receptor-mediated responses. Tumor promoter studies with mixtures of PCDDs and halogenated biphenyls have shown additive, synergistic, and antagonistic effects. To analyse the interactions of TCDD and PCBs as tumor promoters in more detail, we established an in vitro assay, i.e., the enhancement (promotion) of malignant transformation of carcinogen-initiated C3H/M2 mouse fibroblasts after treatment with tumor promoters. The coplanar PCB 126, a potent Ah receptor agonist, and the diortho-substituted PCB153, to which no TEF value has been ascribed, are promoters of malignant transformation. A defined mixture of PCB126 and TCDD had an additive promoting effect, while PCB 153 antagonized the TCDD-mediated promotion. Thus, the TEF-approach may be insufficient to estimate the tumor-promoting activities of PCDDs, PCDFs, and PCBs in mammalian tissues in which diortho-substituted PCBs are greatly accumulated.     

Levels of dioxins, dibenzofurans, PCB and DDE congeners in pooled food samples collected in 1995 at supermarkets across the United States

Food, particularly dairy products, meat, and fish, has been identified as the primary immediate source of intake of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) for the general population. We previously reported PCDD/Fs in individual analyses of food samples from a number of countries, including the U.S., the former Soviet Union, and Vietnam. We also previously estimated daily intake of dioxins and related chemicals in Americans at various ages in these reports. In this paper, the levels of dioxins, dibenzofurans, dioxin toxic equivalents (TEQs), selected dioxin-like PCBs, and DDE (a persistent metabolite of DDT) were measured in 12 pooled food samples from over 90 individual specimens collected from supermarkets throughout the United States during 1995. Samples were pooled by food groups and then analyzed. Food samples were collected in Binghamton, New York; Atlanta, Georgia; Chicago, Illinois; San Diego, California; and Louisville, Kentucky. In addition to the meat, dairy, and fish samples, a vegan (all vegetable, fruit and grain, no animal product) diet, was simulated; this showed the lowest level of dioxins.     

Potential for secondary poisoning and biomagnification in marine organisms

For selected priority pollutants, like organochlorine pesticides, PAHs and PCBs, and mercury and cadmium, the transfer along marine food chains was assessed based on monitoring data. Comparison of the acquired body burden for marine fish and the toxicity thresholds for predating marine birds and mammals provides evidence for the relevance of contaminant uptake with the food and the liability for secondary poisoning. As a consequence, contaminant residues in prey organisms (critical body burden) should be used for marine hazard and risk assessments. Evaluations solely from aquatic exposure concentrations are not adequate to account for potential secondary effects in marine ecosystems.     

Dioxin-like and non-dioxin-like toxic effects of polychlorinated biphenyls (PCBs): implications for risk assessment

Polychlorinated biphenyls (PCBs) are persistent, bioaccumulative, and toxic contaminants in the environment. Individual PCB congeners exhibit different physicochemical properties and biological activities that result in different environmental distributions and toxicity profiles. The variable composition of PCB residues in environmental matrices and their different mechanisms of toxicity complicate the development of scientifically based regulations for the risk assessment. In this article various approaches for the assessment of risks of PCBs have been critically examined. Recent developments in the toxic equivalency factor (TEF) approach for the assessment of toxic effects due to dioxin-like PCBs have been examined. PCB exposure studies that describe non-dioxin-like toxic effects, particularly neurobehavioral effects and their effective doses in animals were compiled. A comparative assessment of effective doses for dioxin-like and non-dioxin-like effects by PCBs has been made to evaluate the relative significance of non-ortho-and ortho-substituted PCBs in risk assessment. Using mink as an example, relative merits and implications of using TEF and total PCB approaches for assessing the potential for toxic effects in wildlife was examined. There are several advantages and limitations associated with each method used for PCB risk assessment. Toxic effects due to coplanar PCBs occur at relatively smaller concentrations than those due to non-dioxin-like PCBs and therefore the TEF approach derives the risk assessment of PCBs, in the environment. The need for the refinement of TEF approach for more accurate assessment of risks is discussed.     

PCBs as environmental estrogens: turtle sex determination as a biomarker of environmental contamination

Polychlorinated biphenyls (PCBs) are widespread, low-level environmental pollutants associated with adverse health effects such as immune suppression and teratogenicity. There is increasing evidence that some PCB compounds are capable of disrupting reproductive and endocrine function in fish, birds, and mammals, including humans, particularly during development. Research on the mechanism through which these compounds act to alter reproductive function indicates estrogenic activity, whereby the compounds may be altering sexual differentiation. Here we demonstrate the estrogenic effect of some PCBs by reversing gonadal sex in a reptile species that exhibits temperature-dependent sex determination.     

Profiles of Great Lakes critical pollutants: a sentinel analysis of human blood and urine. The Great Lakes Consortium

To determine the contaminants that should be studied further in the subsequent population-based study, a profile of Great Lakes (GL) sport fish contaminant residues were studied in human blood and urine specimens from 32 sport fish consumers from three Great Lakes: Lake Michigan (n = 10), Lake Huron (n = 11), and Lake Erie (n = 11). Serum was analyzed for 8 polychlorinated dioxin congeners, 10 polychlorinated furan congeners, 4 coplanar and 32 other polychlorinated biphenyl (PCB) congeners, and 11 persistent chlorinated pesticides. Whole blood was analyzed for mercury and lead. Urine samples were analyzed for 10 nonpersistent pesticides (or their metabolites) and 5 metals. One individual was excluded from statistical analysis because of an unusual exposure to selected analytes. Overall, the sample (n = 31) consumed, on average, 49 GL sport fish meals per year for a mean of 33 years. On average, the general population in the GL basin consume 6 meals of GL sport fish per year. The mean tissue levels of most persistent, bioaccumulative compounds also found in GL sport fish ranged from less than a twofold increase to that of PCB 126, which was eight times the selected background levels found in the general population. The overall mean total toxic equivalent for dioxins, furans, and coplanar PCBs were greater than selected background levels in the general population (dioxins, 1.8 times; furans, 2.4 times; and coplanar PCBs, 9.6 times). The nonpersistent pesticides and most metals were not identified in unusual concentrations. A contaminant pattern among lake subgroups was evident. Lake Erie sport fish consumers had consistently lower contaminant concentrations than consumers of sport fish from Lake Michigan and Huron. These interlake differences are consistent with contaminant patterns seen in sport fish tissue from the respective lakes; GL sport fish consumption was the most likely explanation for observed contaminant levels among this sample. Frequent consumers of sport fish proved to be effective sentinels for identifying sport fish contaminants of concern. In the larger study to follow, serum samples will be tested for PCBs (congener specific and coplanar), DDE, dioxin, and furans.     

Species and organ dependence of PCB contamination in fish, foxes, roe deer, and humans

According to previous experimental results, PCBs are deposited in muscle fat in animals and in humans, although they also reach the brain, the liver, and the lungs. The aim of the present study was to determine the concentrations of the so-called "indicator PCBs" (PCB nos. 28, 52, 101, 138, 153, 180), as described by the German ordinance for maximum concentrations of contaminants in foodstuffs, in muscle tissue, liver, and brain of four different species: fish, fox, roe deer, and humans, all exposed to PCBs directly in their environment. Potential target organs for the accumulation of these congeners were also to be identified. Furthermore, the organs or tissues were to be identified in which PCBs are accumulated, and unusual patterns of accumulation or breakdown of particular PCBs, for example the "dioxin-like PCBs" (coplanar PCBs) determined. For humans, the lungs were also included in these studies. Statistical comparison of PCB concentrations in samples from wild animals and humans showed that in spite of its relatively high fat concentration, brain tissue in all of the species examined (with the exception of fish) appeared to be better protected against accumulation of PCB than liver or muscle tissue. This protection may be the result of the blood-brain barrier, as witnessed by the relatively uniform concentration of PCBs throughout the various organs of fish, since the blood-brain barrier of fish is considerably less efficient than that of mammals. No peculiarities were found in regard to distribution of the coplanar PCBs over the other congeners in this study. This applies to the brain and other organs or tissues of the four species that were examined. Accumulations of PCBs and coplanar PCBs in the liver were only found in fox and roe deer. In contrast, humans were found to have accumulations of the high-chlorinated biphenyls studied here as well as PCB no. 118 in muscle tissue fat and not in the liver. Unexpectedly, low-chlorinated biphenyls were found to accumulate in the human lung. The results of this study show that the lung represents a target organ for the accumulation of potentially metabolically activated low-chlorinated biphenyls, indicating that the possible biological effects of PCBs on the lungs will need to receive more attention in the future.     

Consumption of fatty fish from the Baltic Sea and PCB in whole venous blood, plasma and cord blood from delivering women in the Aland/Turku archipelago

The present study aimed to assess the role of fish consumption for the body burden of polychlorinated biphenyls (PCBs) in mothers living in the Aland and Turku archipelago in Finland. The overall objective was to investigate whether there exists an appropriate population for a full-scale prospective study on PCB-related developmental effects in infants. Concentrations of the four major PCBs were determined in whole venous blood and cord blood from 30 delivering mothers, of which 20 subjects consumed fatty fish from the Baltic Sea (2.5-12.5 meals per month) and the remaining 10 mothers did not. The concentrations of CB-118, CB-138, CB-153, and CB-180 in cord blood were generally two- to threefold lower than in whole blood from the mothers, but strong correlations were observed between PCBs in the two matrices (r = .67-.80). Neither the venous blood nor cord blood concentrations of PCBs, however, were correlated with stated fish intake. Moreover, the concentration of CB-153 in plasma was only weakly associated with fish intake, and the level of organic mercury in erythrocytes was not correlated with fish intake at all. The present results of CB-153 concentrations in women's blood are lower than those reported in other recent investigations. A reasonable contributing explanation is the rapid decline during the last decades of PCB in Baltic Sea fish, which has resulted in less impact of fish intake on the body burdens of PCB in relatively young women (median 30 yr in the present study) as compared with older females. The relatively low PCB levels in blood taken together with the low number of yearly deliveries in the archipelago population makes it an inappropriate study base for a prospective study of PCB-related health effects in infants.     

Multigenerational study of the effects of consumption of PCB-contaminated carp from Saginaw Bay, Lake Huron, on mink. 2. Liver PCB concentration and induction of hepatic cytochrome P-450 activity as a potential biomarker for PCB exposure

This study examined the effect of polychlorinated biphenyls (PCBs) from Saginaw Bay (Lake Huron) carp on the hepatic cytochrome P-450 activity in mink (Mustela vison). Hepatic cytochrome P-450 activities are of interest for their possible use as biomarkers to indicate consumption and biological effects of PCBs in the environment. Adult mink were fed diets containing ocean fish (control diet, 0.0 ppm) or Saginaw Bay carp toprovide 0.25, 0.5, or 1.0 ppm PCBs. Mink were bred after 3 mo of exposure, and half of the parental mink (P1) and kits (F1-1) previously consuming diets containing Saginaw Bay carp were switched to control diet at weaning of the F1-1 kits. P1 and F1-1 mink were then bred within their age and dietary groups after 15 mo of exposure, to produce the second-year F1 (F1-2) and F2 kits. Mink were killed when the new kits were weaned. Transfer of half the animals to the control diet examined whether the effects of the PCB-containing diet on hepatic cytochrome P-450 activity were permanent. Continual exposure to diets containing PCBs from Saginaw Bay carp induced cytochrome P-450 activity in a generally dose-dependent manner. Cytochrome P-450 activity was not different from untreated controls in animals switched to the control diet from the PCB-containing diet. The response of cytochrome P-4501A1 (EROD) activity in a dose-dependent manner and the lack of induction after transfer to noncontaminated diets suggest that this hepatic enzyme activity is a potential biomarker for current exposure to PCBs and other similar cytochrome P-450 inducers.     

Polychlorinated biphenyl (PCB) and dichlorodiphenyl dichloroethylene (DDE) exposure among Native American men from contaminated Great Lakes fish and wildlife

The New York State Department of Health is performing an investigation of Mohawk men, women, and infants who live at the Akwesasne Reserve along the St. Lawrence River in New York, Ontario, and Quebec Three large industrial facilities bordering the Akwesasne Reserve have seriously contaminated the soil and the sediments and fish of the adjacent St. Lawrence River with polychlorinated biphenyls (PCBs). The main study goals are to investigate the associations among the consumption of locally caught fish, residential exposure, body burdens of PCBs, and liver enzyme induction. Contamination with PCBs, polychlorinated dibenzofurans, polychlorinated dibenzodioxins, polyaromatic hydrocarbons, dichlorodiphenyl dichloroethylene (DDE) and other chemicals has been documented in locally caught fish, ducks, and other wildlife. The contamination of fish and wildlife is a major concern of the Mohawk people, since their tradition and culture emphasize the interdependence of man and his environment and because many residents formerly depended heavily on local fish and waterfowl for food. The focus of this research from 1986-1992 was on nursing women and infants. The major purpose of the current project is to determine if there are associations between dietary, residential, and occupational exposures to PCBs and DDE and individual body burdens in Mohawk men, specifically the husbands, partners, fathers, brothers, or other male relatives of the women in our other studies. In other fish-eating populations, adult men have tended to demonstrate higher PCB and DDE body burdens than women and children. Exposure estimates based on the reported consumption of locally caught fish and wildlife and residential histories will be correlated with the specific pattern of PCB congeners found in serum, thereby establishing a direct relationship between two potential sources of exposure and body burdens. Liver function will be examined through the caffeine breath test (CBT), a sensitive, noninvasive method of assessment of enzyme induction, one of the earliest detectable biological responses to PCBs in laboratory animals. This test appears promising as a method to detect subtle subclinical effects before the onset of overt clinical symptoms. The project is among the first to explore differences in dietary and other exposures, body burdens, and potential adverse health effects due to specific PCB congeners in men and women from the same source population.     

Impaired place learning and unimpaired cue learning in hippocampal-lesioned pigeons.

Hippocampal processing is often crucial for normal spatial learning and memory in both birds and mammals, suggesting a general similarity in avian and mammalian hippocampal function. However, few studies using birds have examined the effect of hippocampal lesions on spatial tasks analogous to those typically used with mammals. Therefore, we examined how hippocampal lesions would affect the performance of pigeons in a dry version of the water maze. Experiment 1 showed that hippocampal-lesioned birds were impaired in acquiring the location of hidden food in the maze. Experiment 2 showed that hippocampal-lesioned birds were not impaired when a single cue indicated the location of hidden food. These results support the notion that avian and mammalian hippocampal functions are quite similar, in terms of the tasks for which their processing is crucial and the tasks for which it is not. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do endurance sports lead to osteoporosis in women?

Highly contaminated Lake Ontario sport fish represent an important human dietary exposure to polychlorinated biphenyls (PCBs) and other toxic contaminants that may disrupt endocrine pathways. New York State Angler Cohort women interviewed by telephone in 1993 provided menstrual cycle length (n = 2,223). Fish consumption at cohort enrollment in 1991 was categorized by duration and frequency and was used to calculate a PCB exposure index. Multiple regression analyses identified significant cycle length reductions with consumption of more than one fish meal per month (1.11 days) and moderate/high estimated PCB index (-1.03 days). Women who consumed contaminated fish for 7 years or more also had shorter cycles (-0.63 days).     

Identification of a cellular receptor for subgroup E avian leukosis virus

Genetic studies in chickens and receptor interference experiments have indicated that avian leukosis virus (ALV)-E may utilize a cellular receptor related to the receptor for ALV-B and ALV-D. Recently, we cloned CAR1, a tumor necrosis factor receptor (TNFR)-related protein, that serves as a cellular receptor for ALV-B and ALV-D. To determine whether the cellular receptor for ALV-E is a CAR1-like protein, a cDNA library was made from turkey embryo fibroblasts (TEFs), which are susceptible to ALV-E infection, but not to infection by ALV-B and ALV-D. The cDNA library was screened with a radioactively labeled CAR1 cDNA probe, and clones that hybridized with the probe were isolated. A 2.3-kb cDNA clone was identified that conferred susceptibility to ALV-E infection, but not to ALV-B infection, when expressed in transfected human 293 cells. The functional cDNA clone is predicted to encode a 368 amino acid protein with significant amino acid similarity to CAR1. Like CAR1, the TEF protein is predicted to have two extracellular TNFR-like cysteine-rich domains and a putative death domain similar to those of TNFR I and Fas. Flow cytometric analysis and immunoprecipitation experiments demonstrated specific binding between the TEF CAR1-related protein and an immunoadhesin composed of the surface (SU) envelope protein of subgroup E (RAV-0) virus fused to the constant region of a rabbit immunoglobulin. These two activities of the TEF CAR1-related protein, specific binding to ALV-E SU and permitting entry only of ALV-E, have unambiguously identified this protein as a cellular receptor specific for subgroup E ALV.     

Definitive localization of isolated tracheoesophageal fistula using bronchoscopy and esophagoscopy for guide wire placement

PURPOSE: To aid in identification of isolated tracheoesophageal fistulas (TEF), many surgeons have recommended the bronchoscopic placement of a ureteric or Fogarty catheter. This method can fail because of intraoperative dislodgment of the catheter. The authors present a new technique that enables us to definitively isolate and treat all H-type fistulas. METHODS: Six cases of isolated TEF are presented consisting of 4 H-type fistulas, a proximal pouch fistula, and a recurrent TEF. Three of the patients had undergone a total of four prior failed operations at outside institutions using attempted bronchoscopic catheter placement. On all six patients, bronchoscopy was first performed where the fistula tract was noted in the trachea and a guide wire was passed through the fistula. After orotracheal intubation, the authors performed rigid esophagoscopy; the guide wire was identified and brought out through the mouth. This created a wire loop through the fistula. With the use of x-ray we were then able to visualize the level of the fistula and determine whether a cervical or thoracic approach should be used. Identification of the fistula intraoperatively was then facilitated by traction on the loop by the anesthesiologist. RESULTS: Five of the six TEFs were repaired with neck exploration; one required right thoracotomy. In all patients, the fistula was identified and divided. There were no recurrences or other complications. CONCLUSION: This new technique is a simple and definitive method in identification and treatment of isolated TEF.     

A prospective randomised study of local versus general anaesthesia for cataract surgery

A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that the majority of PCBs are likely to interact with AhR in their nonplanar conformations. In addition, we demonstrate that the affinities of PCBs for AhR relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding toxic equivalency factors in animals. The reported methodology is likely to be applicable to other polyhalogenated and mixed polyhalogenated bi- and terphenyls and related xenobiotics; thus, it could minimize the number of in vivo studies in laboratory animals and facilitate the identification of potentially hazardous aromatic xenobiotics.     

Increased concentrations of octachlorodibenzo-p-dioxin in cases with breast cancer--results from a case-control study

Organochlorines are persistent and highly lipophilic environmental contaminants which bioaccumulate in the food chain. Some of these chemicals, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), have been suggested to be of significance in the aetiology of breast cancer. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an anti-oestrogen in animal studies and should be thus lower the risk of breast cancer. The other isomers of polychlorinated dibenzo-p-dioxins (PCDDs) or the chemically related polychlorinated dibenzofurans (PCDFs) have not been tested regarding carcinogenesis of the breast. The purpose of this study was to investigate whether PCDDs or PCDFs influence the risk for breast cancer. Consecutive patients who underwent surgery for a breast disease between 1993 and 1995 were recruited for the study. Cases were 22 patients with infiltrative breast cancer and controls were 19 patients operated for a benign breast disease during the same time period. Approximately 10 g of breast tissue free from tumour was taken from the specimen and frozen until analysis. Fat was extracted, cleaned and analysed with a high-resolution gas chromatograph coupled to a high-resolution mass spectrometer. Median concentrations of octachlorinated dibenzo-p-dioxin (OCDD) were 598 (170-14,880) and 396 (103-1,847) pg/g lipid in the cases and in the controls, respectively. In a multivariate logistic regression analysis controlling for other risk factors for breast cancer increased odds ratio (OR) was obtained for OCDD: 401-1000 pg/g lipid yielded OR 3.8, 95% confidence interval (CI) 0.4-39, > 1000 pg/g lipid gave OR 5.2, CI 0.4-72. When the lipid OCDD variable was examined as a continuous risk factor there was a 1.09 (9%), CI 0.95-1.25, increase in the adjusted OR for breast cancer per 100 unit (pg/g lipid) increase in OCDD. No differences were found between cases and controls for the other six tested PCDDs. Mean concentration of TCDD was in the cases 3.6 (1.0-7.9) and in the controls 3.3 (1.1-6.3) pg/g lipid. For PCDFs no significant differences were found between cases and controls. The results were not changed if oestrogen or progesterone receptor status, S-phase fraction and DNA ploidy were considered. Breast tissue concentration of OCDD was increased in cancer patients, whereas the concentrations of other PCDDs and PCDFs were equal in cases and controls.     

Polychlorinated diphenyl ethers, dibenzo-p-dioxins, dibenzofurans and biphenyls in seals and sediment from the Gulf of Finland

Polychlorinated diphenyl ethers (PCDEs), 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) were analyzed in seals from the Gulf of Finland and in sediments from the Gulf of Finland and near Gotland. The sediments included one surface core from both sampling sites. The seal material consisted of 14 ringed seals and 6 grey seals that all were found dead and examined for pathology. The main aims were to scrutinize levels and patterns of PCDEs for the first time in seals from the Baltic Sea and to estimate whether chlorinated compounds mentioned have an influence on an exceptional high mortality that occurred among ringed seals in the Gulf of Finland in late 1991. The concentrations of 50 congeners of tetra- through deca-CDEs analyzed ranged from < 0.3 to 62 ng/g lipid weight (lw) in seal blubber, but in the sediments PCDEs were non-detectable (tetra- through hepta-CDEs < 0.1 ng/g dry weight (dw)). In ringed seals with good nutritional status, the concentrations of almost all PCDE congeners were greater in two adult females than in specimens of younger age groups. The concentrations of PCDDs and PCDFs as TCDD-equivalents exceeded those of the coplanar (non-ortho) PCBs in sediments, whereas non- and monoortho PCBs constituted greater toxic loads as those calculated for PCDDs and PCDFs in seals. However, the levels revealed do not explain the high mortality of ringed seals.     

Congener-specific levels of dioxins and dibenzofurans in U.S. food and estimated daily dioxin toxic equivalent intake

Food, especially meat, milk, and fish, is the immediate source of almost all polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxinlike compounds in the general population. To estimate intake of these highly toxic compounds, we performed congener-specific dioxin analyses for the first time on U.S. food for 18 dairy meat, and fish samples from a supermarket in upstate New York. 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD, "dioxin") toxic equivalents (TEqs) on a wet weight basis for the dairy products ranged for 0.04 to 0.7 ppt, meat TEqs ranged from 0.03 to 1.5 ppt, and fish TEqs ranged from 0.02 to 0.13 ppt. Previous human breast milk and infant formula analyses were used with the current preliminary food data to estimate a range of dioxin intake for Americans. Average daily food intake of TEqs for an adult weighing 65 kg was estimated to be between 0.3 and 3.0 pg/kg body weight, for a total of 18-192 pg TEq, using 1986 American consumption rates. Due to the relatively high level of PCDDs and PCDFs commonly found in human breast milk from American women and from women in other industrial countries, a nursing infant may consume an average of 35-53 pg TEq/kg body weight/day in its first year of life. This may be compared with the current U.S. EPA virtually safe dose of 0.006 pg TCDD/kg body weight per day over a 70-year lifetime based on an upper limit cancer risk of 10(-6), or the 10 pg/kg/day used by some European government agencies.     

Sertoli cells in culture and mRNA differential display provide a sensitive early warning assay system to detect changes induced by xenobiotics

We have used cultured rat Sertoli cells as an "early warning system" to monitor for morphological and biochemical changes induced by two different xenobiotics-cadmium acetate and polychlorinated biphenyls (PCBs). Sertoli cells begin to round, become vacuolized, and detach from their substrate within 24 hours of culture in the presence of cadmium at concentrations of 0.5-1.0 microM. Similar results were obtained with a lower dose of cadmium (0.01 microM) after 72 hours. When Sertoli cells are cultured for 24 hours in the presence of a mixture of PCBs (3,3',4,4'-tetrachlorobiphenyl, 2,2',4,6,6'-pentachlorophenyl, and 2,2',3,3',4,5,5', 6,6'-nonachlorobiphenyl) at concentrations of 1.0-2.0 microM, they enlarge. After 72 hours, a lower dose of PCBs (0.01 microM) produces similar cellular enlargement. Despite their changes in morphology, no reduction in Sertoli cell viability was seen at any of the concentrations or time points studied for either toxicant. Using mRNA differential display, a number of novel cDNAs were detected when cells were cultured with either cadmium or the PCBs, demonstrating that changes in gene expression accompany the changes in Sertoli cell structure. We propose that Sertoli cells in culture and mRNA differential display provide a sensitive morphological and biochemical assay system to detect early direct effects of low concentrations of toxicants on mammalian Sertoli cells.