Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction - a population-based prospective cohort study.

BACKGROUND: Fish consumption may promote cardiovascular health. The role of major food contaminants, such as polychlorinated biphenyls (PCBs) common in fatty fish, is unclear. We assessed the association between dietary PCB exposure and risk of myocardial infarction taking into account the intake of long-chain omega-3 fish fatty acids. METHODS: In the prospective population-based Swedish Mammography Cohort, 33,446 middle-aged and elderly women, free from cardiovascular disease, cancer and diabetes at baseline (1997) were followed-up for 12 years. Validated estimates of dietary PCB exposure and intake of fish fatty acids (eicosapentaenoic acid and docosahexaenoic acid; EPA-DHA) were obtained via a food frequency questionnaire at baseline. RESULTS: During follow-up 1386 incident cases of myocardial infarction were ascertained through register-linkage. Women in the highest quartile of dietary PCB exposure (median 286 ng/day) had a multivariable-adjusted RR of myocardial infarction of 1.21 (95% confidence interval [CI], 1.01-1.45) compared to the lowest quartile (median 101 ng/day) before, and 1.58 (95% CI, 1.10-2.25) after adjusting for EPA-DHA. Stratification by low and high EPA-DHA intake, resulted in RRs 2.20 (95% CI, 1.18-4.12) and 1.73 (95% CI, 0.81-3.69), respectively comparing highest PCB tertile with lowest. The intake of dietary EPA-DHA was inversely associated with risk of myocardial infarction after but not before adjusting for dietary PCB. CONCLUSION: Exposure to PCBs was associated with increased risk of myocardial infarction, while some beneficial effect was associated with increasing EPA and DHA intake. To increase the net benefits of fish consumption, PCB contamination should be reduced to a minimum.

N-acetylcysteine (NAC) diminishes the severity of PCB 126-induced fatty liver in male rodents.

Potent aryl hydrocarbon receptor agonists like PCB 126 (3,3',4,4',5-pentachlorobiphenyl) cause oxidative stress and liver pathology, including fatty liver. Our question was whether dietary supplementation with N-acetylcysteine (NAC), an antioxidant, can prevent these adverse changes. Male Sprague-Dawley rats were fed a standard AIN-93G diet (sufficient in cysteine) or a modified diet supplemented with 1.0% NAC. After one week, rats on each diet were exposed to 0, 1, or 5µmol/kg body weight PCB 126 by i.p. injection (6 rats per group) and euthanized two weeks later. PCB-treatment caused a dose-dependent reduction in growth, feed consumption, relative thymus weight, total glutathione and glutathione disulfide (GSSG), while relative liver weight, glutathione transferase activity and hepatic lipid content were dose-dependently increased with PCB dose. Histologic examination of liver tissue showed PCB 126-induced hepatocellular steatosis with dose dependent increase in lipid deposition and distribution. Dietary NAC resulted in a reduction in hepatocellular lipid in both PCB groups. This effect was confirmed by gravimetric analysis of extracted lipids. Expression of CD36, a scavenger receptor involved in regulating hepatic fatty acid uptake, was reduced with high dose PCB treatment but unaltered in PCB-treated rats on NAC-supplemented diet. These results demonstrate that NAC has a protective effect against hepatic lipid accumulation in rats exposed to PCB 126. The mechanism of this protective effect appears to be independent of NAC as a source of cysteine/precursor of glutathione.

Evaluating daily exposure to polychlorinated biphenyls and polybrominated diphenyl ethers in fish oil supplements.

Fish oil supplements have become a popular means of increasing one's dietary intake of essential polyunsaturated fatty acids. However, there is growing concern that the levels and potential health effects of lipophilic organic contaminants such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may diminish some of the health benefits associated with the daily consumption of fish oil supplements. In this study, ten over-the-counter fish oil supplements available in the United States were analysed for PCBs and PBDEs and daily exposures calculated. Based on manufacturers' recommended dosages, daily intakes of PCBs and PBDEs ranged from 5 to 686 ng day(-1) and from 1 to 13 ng day(-1), respectively. Daily consumption of fish oil supplements expose consumers to PCBs and PBDEs. However, in comparison with fish ingestion, fish supplements may decrease daily PCB exposure and provide a safer pathway for individuals seeking to maintain daily recommended levels of polyunsaturated fatty acids.

Acute toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in male Sprague-Dawley rats: effects on hepatic oxidative stress, glutathione and metals status.

Although polychlorinated biphenyl (PCBs) production, and new uses for PCBs, was halted in the 1970s in the United States, PCBs continue to be used in closed systems and persist in the environment, accumulating in fatty tissues. PCBs are efficacious inducers of drug metabolism and may increase oxidative events and alter many other biochemical and morphologic parameters within cells and tissues. The goal of the present study was to evaluate the effects of a single, very low dose of PCB 126 (3,3',4,4',5-pentachlorobiphenyl), a coplanar, dioxin-like PCB congener and aryl hydrocarbon receptor (AhR) agonist, on redox status, metals homeostasis, antioxidant enzymes, and cellular morphology. To examine these parameters, male Sprague-Dawley rats were fed a purified AIN-93 basal diet containing 0.2 ppm selenium for two weeks, then administered a single i.p. injection of corn oil (5 ml/kg body weight) or 1µmol PCB 126/kg body weight (326µg/kg body weight) in corn oil. Rats were maintained on the diet for an additional two weeks before being euthanized. This dose of PCB 126 did not alter feed intake or growth, but significantly increased liver weight (42%) and hepatic microsomal cytochrome P-450 (CYP1A) enzyme activities (10-40-fold increase). Hepatic zinc, selenium, and glutathione levels were significantly decreased 15%, 30%, and 20%, respectively, by PCB 126. These changes were accompanied by a 60% decrease in selenium-dependent glutathione peroxidase activity. In contrast, hepatic copper levels were increased 40% by PCB 126. PCB 126-induced pathology was characterized by hepatocellular hypertrophy and mild steatosis in the liver and a mild decrease in cortical T-cells in the thymus. This controlled study in rats fed a purified diet shows that even a single, very low dose of PCB 126 that did not alter feed intake or growth, significantly perturbed redox and metals homeostasis and antioxidant and enzyme levels in rodent liver.

Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat: Part 1: Effects on somatic growth, growth hormone-axis activity and bone mass in the offspring.

Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure. Dams were treated during pregnancy from GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.

Dioxins and polychlorinated biphenyls (PCBs) in fish oil dietary supplements: occurrence and human exposure in the UK.

Commercially available fish oil supplements sourced from retail outlets in the UK, as well as by mail order, were surveyed in 2000-02 for dioxin (PCDD/Fs) and polychlorinated biphenyl (PCB) content. Sampled products were representative of market share. The WHO-TEQ values for these products ranged from 0.18 to 8.4 ng kg-1 for SigmaPCDD/F and from 1.1 to 41 ng kg-1 for Sigma dioxin-like PCBs. The results suggest a downward trend in the levels of dioxins in fish oil supplements over the last decade, since levels for similar products ranged from 0.3 to 10 ng kg-1 for SigmaPCDD/F WHO-TEQ in 1996. Levels of ICES (International Council for the Exploration of the Seas) 7 PCBs in the current study ranged from 8.3 to 267 microg kg-1. Subsequent to this survey, European Union legislation has been introduced that includes a maximum limit of 2 ng kg-1 WHO-TEQ for dioxins in fish oil products for human consumption. Twelve of the 33 products reported here would have exceeded this limit. Negotiations are in progress to incorporate dioxin-like PCBs into the European Union regulations. When manufacturer-recommended doses were applied to the observed levels, the estimated upper bound human exposure to dioxins and dioxin-like PCBs from dietary intake of these products ranged from 0.02 to 7.1 pg WHO-TEQ kg-1 body weight day-1 for adults and from 0.02 to 10 pg WHO-TEQ kg-1 body weight day-1 for schoolchildren. This level rises to 1.8-8.9 pg WHO-TEQ kg-1 body weight day-1 for adults and 1.4-14 pg WHO-TEQ kg-1 body weight day-1 for schoolchildren when combined with the average exposure from the whole diet in 1997. Again, subsequent to this survey, the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) revised the UK tolerable daily intake (TDI) for mixtures of dioxins and dioxin-like PCBs from 10 to 2 pg WHO-TEQ kg-1 body weight day-1. This is in line with the tolerable weekly intake (TWI) of 14 pg WHO-TEQ kg-1 body weight set by the Scientific Committee on Food (SCF).

Effects of gender, diet, exogenous melatonin and subchronic PCB exposure on plasma immunoglobulin G in mink.

Effects of different fish-based diets (freshwater smelt, Baltic herring, marine herring/cod offal or their mixtures), gender, beta-glucan supplement, exogenous melatonin, and PCB exposure (Aroclor 1242((R)), 1 mg per animal per day in feed) on plasma immunoglobulin G (IgG) in the mink (Mustela vison) were studied. The aims of the study were to find out whether plasma IgG of the mink is affected by the subchronic PCB exposure, and whether biological, nutritional and hormonal effects are large enough to mask the possible IgG response. The concentration of IgG was determined using enzyme-linked immunosorbent assay (ELISA). Sexual dimorphism was detected, the males having higher levels of plasma IgG. In addition, melatonin tended to decrease IgG in females but not males. Diet also affected the humoral immune arm; the mixed-fish diets caused an unfavorable ratio of the oxidation products of lipids vs. vitamin E in liver, and resulted in low IgG concentration in plasma. In males fed Baltic herring, the beta-glucan supplement also lowered IgG levels. The PCBs failed to affect the plasma IgG of the smelt-fed female mink, and IgG concentration was not correlated with increased hepatic EROD activity or with the decreased total retinol in the liver of exposed mink. It is concluded that hormonal/seasonal and dietary factors affect the plasma IgG levels to such an extent that possible change in plasma IgG level due to PCBs in wild populations of mink is difficult to detect without a large amount of reference data.

Dietary taurine alters ascorbic acid metabolism in rats fed diets containing polychlorinated biphenyls.

The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P < 0.01). In PCB-fed rats, urinary ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.

Toxic potency of 3,3',4,4',5-pentachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat.

Toxic and biochemical potencies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) were studied relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a 13-week feeding study in female Sprague-Dawley rats. To study possible interactive effects the combinations of both compounds were administered. The diets were supplemented with PCB 126 (7, 50, or 180 micrograms/kg diet), with TCDD (0.4 or 5 micrograms/kg diet), or with combinations of both compounds. An estimated daily intake of 0.47 micrograms PCB 126/kg body weight/day caused thymic atrophy, a dramatic loss in hepatic retinoids, and a marked induction in CYP1A1 and CYP1A2 activities. At a daily intake of 3.18 micrograms PCB 126/kg body weight/day a decrease in body weight gain, liver enlargement, and plasma thyroid hormone concentrations occurred. Based on a simultaneous subchronic feeding study with TCDD, a toxic equivalency factor range between 0.01 and 0.1 was estimated for PCB 126 for the mentioned effects. Antagonism was found between TCDD and PCB 126 for hepatic retinol levels and CYP1A2 activity. At the same time, TCDD and PCB 126 liver residue levels were slightly decreased by coadministration. However, these antagonistic effects occurred at maximum induction levels of CYP1A1 and CYP1A2, which are not likely to occur at levels relevant for humans.

Toxic potency of 2,3,3',4,4',5-hexachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat.

Interactive effects on toxicity and biochemical parameters were studied between 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a 13-week feeding study of female Sprague-Dawley rats. The diets were supplemented with PCB 156 (1.2, 6, or 12 mg/kg), with TCDD (5 micrograms/kg), or with combinations of both compounds. Estimated daily intake of 365 micrograms/kg body wt/day (6 mg/kg diet group) of PCB 156 caused a decrease in body weight gain, thymic atrophy, liver enlargement, a loss in hepatic retinoids, induction of CYP2B activity, and a decrease in plasma thyroxine concentrations. At an estimated daily intake of 81 micrograms PCB 156/kg body wt/day CYP1A1 and CYP1A2 activities were induced. Compared to a simultaneous subchronic feeding study with TCDD a toxic equivalency factor (TEF) between 0.00004 and 0.001 was estimated for PCB 156 with respect to the mentioned effects. Antagonistic effects were found between TCDD and PCB 156 for CYP2B activity and hepatic retinol levels. These effects concurred with a PCB 156 dose-dependent decrease in hepatic TCDD levels. Hepatic PCB 156 levels were found to be increased at the 1.2-mg PCB 156/kg dose group in coadministration with TCDD. In conclusion, at least part of the antagonistic effects between PCB 156 and TCDD observed have a toxico-kinetic base. Furthermore, the magnitude of the antagonistic effects may be neglected in comparison with the uncertainty in the TEF value. Therefore, the interactive effects found between PCB 156 and TCDD may have no implications for the additivity of the TEF concept.

Determination of polychlorinated biphenyl levels in the serum of residents and in the homogenates of seafood from the New Bedford, Massachusetts, area: a comparison of exposure sources through pattern recognition techniques.

We measured the residues of polychlorinated biphenyls (PCBs) in the serum of 23 residents of the New Bedford, Massachusetts, area and from two homogenates each of bluefish and lobsters from the same area. We used congener-specific and total Aroclor quantitative approaches, both of which involved gas chromatography with electron capture detection. Using gas chromatography mass spectrometry (electron ionization mode), we confirmed the presence of PCBs in the combined serum samples and in the aliquots of bluefish and lobsters. In measuring the PCB levels in serum, we found good agreement between the two electron capture detector approaches (r > or = 0.97) when the serum of specific congeners was compared to total Aroclor. We used univariate and multivariate quality control approaches to monitor these analyses. Analytical results for bluefish showed a better agreement between the two techniques than did those for lobsters; however, the small number of samples precluded any statistical comparison. We also measured levels of chlorinated pesticides in the serum samples of two groups of New Bedford residents, those with low PCB levels (< 15 ng/ml) and those with high PCB levels (> or = 15 ng/ml). We found that residents with high PCB levels also tended to have higher levels of hexachlorobenzene (HCB) and 1,1-dichloro-2,2-di-(p-chlorophenyl) ethylene (p,p'-DDE). The higher concentration of all three analytes appears to be influenced by employment in the capacitor industry, by seafood consumption, or both. Using Jaccard measures of similarity and principal component analysis we compared the gas chromatographic patterns of PCBs found in the serum of New Bedford area residents with high serum PCBs with the patterns found in homogenates of lobsters (inclusive of all edible portions except the roe), in homogenates of bluefish fillets taken from local waters, and in serum from goats fed selected technical Aroclors (e.g. Aroclors 1016, 1242, 1254, or 1260). The patterns found in human serum samples were similar to the patterns found in lobster homogenates. Both of these patterns closely resembled patterns found in the serum samples of the goat fed aroclor 1254, as demonstrated by both pattern recognition techniques. In addition, the chromatographic patterns of human serum and of lobsters and bluefish homogenates all indicated the presence of PCBs more characteristic of Aroclors 1016 or 1242.

Effect of prototypic polychlorinated biphenyls on hepatic and renal vitamin contents and on drug-metabolizing enzymes in rats fed diets containing low or high levels of retinyl palmitate.

Two groups of weanling male Sprague-Dawley rats fed a diet supplemented with either 0.6 or 6 retinol equivalents/g diet were each separated into three further groups receiving 300 mumol 2,2',4,4',5,5'-hexachlorobiphenyl/kg body weight, 300 mumol 3,3',4,4'-tetrachlorobiphenyl kg/body weight or vehicle only (corn oil). Only the coplanar (3,4)2Cl congener caused a slight reduction in food intake, thymic atrophy and led to a significant decrease in the liver vitamin A storage. The vitamin A lost by the liver was approximately the same in both dietary groups; however an increased renal accumulation of vitamin A was observed in the high vitamin A group. Serum retinol was reduced by (3,4)2Cl treatment but remained unchanged by (2,4,5)2Cl exposure. Total amounts of ascorbic acid and its oxidation products were increased in the liver and in the kidney by both xenobiotics while niacin and thiamine concentrations were lowered by (3,4)2Cl only. Microsomes from vitamin A-deficient rats exhibited a marked decrease in the anisotropy parameter. After (2,4,5)2Cl exposure, an increase in membrane fluidity was observed linked to a decrease in cholesterol/phospholipid (C/P) ratio. Treatment with (3,4)2Cl caused a significant decrease in the index of fluorescence polarization only in the low vitamin A group even if the C/P ratio was enhanced in both dietary groups. This study shows that the polychlorinated biphenyl with the 3-methylcholanthrene-type pattern of induction of cytochrome P-450 has more profound effects on B group vitamins and particularly vitamin A homeostasis than does the phenobarbital-type inducer. Moreover, this situation, which has been found to be similar to that in vitamin A deficiency, is not ameliorated by a high dietary vitamin A intake.

[The effect of polyclorinated biphenyls in chickens: the effect of short-term administration of high doses of Delor 103 on the levels of thyroxine, triiodothyronine, sodium, potassium and calcium in the blood]. / Ucinek polychlorovaných bifenylu (PCB) na organismus kurat: vliv krátkodobého príjmu vysokých dávek Deloru 103 na koncentraci thyroxinu, trijodthyroninu, sodíku, draslíku a vápníku v krevním séru.

The trial with a short-time receiving (7 days) of high doses of the preparation Delor 103 (PCB) to chickens (1000 mg.kg-1 feed stuffs) had a long-run negative effect on their state of health. Clinical picture of intoxication resembled an involution syndrome. A defect persistence of the conversion of thyroid hormone T4 to T3 was found. Regeneration of T4 hormone production was rather fast. Supplement of hormones T4 and T3 to feed had no significant influence on the course of intoxication, but it caused changes in concentrations of K+, Ca++, and the total calcium in the blood serum of the birds. Simultaneous supplement of Delor 103 moderated the intensity of changes induced by exogenous flow of thyroid hormones. Histological changes were demonstrated in the primary lymph organs, which supported of findings of immunosuppressive effect in PCB. Supplement of the thyreostatic Carbimazol (Carbimazolum/1-carbaetoxy-3-methyl-2-thioimidazolin um) caused no symptoms testifying to hypofunction of thyroid gland in chickens.

Effects of dietary polychlorinated biphenyls on vitamin E and selenium nutrition in the chick.

Experiments were conducted to determine the effects of polychlorinated biphenyls (PCBs) on vitamin E-selenium nutrition in the chick. Results showed that 10 p.p.m. Aroclor¿ 1254 in the diets of breeding S.C.W.L. hens increased the susceptibility of progency to vitamin E-selenium deficiency when those chicks were reared on a diet deficient in vitamin E and supplemented with a marginal level of selenium. Susceptibility to this deficiency, as measured by the incidence of exudative diathesis, was also increased when PCBs were added to chick diets. Dietary PCBs were shown to induce hepatic microsomal benzopyrene hydroxylase and induction of this activity was associated with decreased biological utilization of dietary selenium. PCBs were shown to increase the apparent requirements of the chick for vitamin E and selenium for prevention of exudative diathesis. However, discrimination between effects on vitamin E function and effects on selenium function was not possible in these experiments.