Effect of 3,3',4,4'-tetrachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl on the induction of hepatic lipid peroxidation and cytochrome P-450 associated enzyme activities in rats

Polychlorinated biphenyls (PCBs) are environmental contaminants that have been widely used for various industrial purposes. In spite of numerous studies on PCBs, however, their mechanism of toxicity remains unknown. The role of cytochrome P-450 in PCBs induced hepatic lipid peroxidation is controversial. Therefore, the present study was undertaken to study the mechanism of action of two PCBs and their role in cytochrome P-450 induction and lipid peroxidation, determined in vivo and during the incubation of subcellular fractions. We also examined whether agonist/antagonist activities between the two PCBs were occurring. Two PCBs were studied: 3,3',4,4'-tetrachlorobiphenyl (PCB-77), a non-ortho-substituted, coplanar PCB; and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), a di-ortho-substituted, non-planar PCB. Groups of male Sprague-Dawley rats were given a single i.p. injection of one of the two PCBs (at doses of 30, 150, or 300 micromol/kg), both PCBs (at doses of 30 or 150 micromol/kg), or vehicle alone. Rats were sacrificed after 2, 6, or 24 h; or 2, 6, or 10 days. Cytochrome P-450 induction occurred as early as 2 h with PCB-77 and 24 h with PCB-153. Significant increases in thiobarbituric acid reactive substances (TBARS) content in liver tissue occurred 2, 6 and 10 days after treatment with PCB-77 and PCB-153; it was unclear whether these PCBs were synergistic in their induction of TBARS formation. Liver microsomal fractions incubated with NADPH only showed increased TBARS formation at the highest doses of PCB-77 and PCB-153 after 6 days. The results indicate that both PCBs induced cytochrome P-450 enzymes and enhanced lipid peroxidation in liver and subcellular fractions but with different potencies and onsets of action. The results also indicate a larger time difference between cytochrome P-450 induction and lipid peroxidation for PCB-77. Thus, both PCB-77 and PCB-153 are toxic to cells, but may act via different mechanisms to induce their effects.     

Associations between intrauterine exposure to polychlorinated biphenyls on neonatal ano-genital distance

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus.This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns.Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables.Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns.This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.     

Changes in egg composition of American kestrels exposed to dietary polychlorinated biphenyls

Changes in the quality of eggs of birds exposed to polychlorinated biphenyls (PCBs) have been described, but have never been directly attributed to PCBs. Polychlorinated biphenyl residues in eggs have been associated with reduced reproductive success and embryonic deformities in wild birds. Egg size and composition, specifically the amount of albumen, yolk, and water in an egg, also influence the growth and viability of embryos and hatchlings, and consequently the reproductive success of birds. To deter mine whether PCB exposure of adult birds affected the size and composition of their eggs, 25 pairs of captive American kestrels (Falco sparverius) were fed a mixture of PCB-spiked (1248:1254:1260) food to give an approximate exposure of 7 mg/kg body weight/d, beginning 1 mo prior to pairing, and continuing throughout the courtship, egg-laying, and incubation periods. This dietary level in the adult female kestrels resulted in mean total PCB residues in the eggs of 34.1 microg/g wet weight (geometric mean), which is environmentally relevant. PCB residues in eggs increased with the time of female exposure to the contaminated diet and laying date. Variation in egg size within PCB clutches was significantly greater than within control clutches, although absolute egg mass and volume did not differ markedly by treatment. Only infertile eggs and only one egg per clutch were used for egg composition analysis. Yolks in the PCB-contaminated eggs were heavier, with less wet and dry albumen relative to control eggs. Water content and eggshell thickness were not significantly affected by PCB exposure. These results suggest that eggs from the PCB treatment have relatively more lipid and less protein available for embryonic development. Changes in egg composition were not associated with egg size, lay date, ambient temperature, humidity, or precipitation, which are factors known to affect these variables in bird eggs. The PCB-induced changes in egg composition described here provide insight into possible mechanisms contributing to reduced reproductive performance in wild birds exposed to PCBs.     

CHANGES IN EGG COMPOSITION OF AMERICAN KESTRELS EXPOSED TO DIETARY POLYCHLORINATED BIPHENYLS

Changes in the quality of eggs of birds exposed to polychlorinated biphenyls (PCBs) have been described, but have never been directly attributed to PCBs. Polychlorinated biphenyl residues in eggs have been associated with reduced reproductive success and embryonic deformities in wild birds. Egg size and composition, specifically the amount of albumen, yolk, and water in an egg, also influence the growth and viability of embryos and hatchlings, and consequently the reproductive success of birds. To deter mine whether PCB exposure of adult birds affected the size and composition of their eggs, 25 pairs of captive American kestrels (Falco sparverius) were fed a mixture of PCB-spiked (1248:1254:1260) food to give an approximate exposure of 7 mg/kg body weight/d, beginning 1 mo prior to pairing, and continuing throughout the courtship, egg-laying, and incubation periods. This dietary level in the adult female kestrels resulted in mean total PCB residues in the eggs of 34.1 µg/g wet weight (geometric mean), which is environmentally relevant. PCB residues in eggs increased with the time of female exposure to the contaminated diet and laying date. Variation in egg size within PCB clutches was significantly greater than within control clutches, although absolute egg mass and volume did not differ markedly by treatment. Only infertile eggs and only one egg per clutch were used for egg composition analysis. Yolks in the PCB-contaminated eggs were heavier, with less wet and dry albumen relative to control eggs. Water content and eggshell thickness were not significantly affected by PCB exposure. These results suggest that eggs from the PCB treatment have relatively more lipid and less protein available for embryonic development. Changes in egg composition were not associated with egg size, lay date, ambient temperature, humidity, or precipitation, which are factors known to affect these variables in bird eggs. The PCB-induced changes in egg composition described here provide insight into possible mechanisms contributing to reduced reproductive performance in wild birds exposed to PCBs.     

Dietary accumulation of PCBs from a contaminated sediment source by a demersal fish (Leiostomus xanthurus)

Accumulation and dietary transfer of PCBs from contaminated harbor sediments were studied in a laboratory food chain consisting of sediments, polychaetes (Nereis virens) and a predatory fish (Leiostomus xanthurus). The study was conducted in two phases to distinguish dietary uptake from PCB accumulation resulting from sediment exposure alone. In phase I fish and polychaetes were separately exposed to field-collected PCB contaminated sediments (5.2 μg/g dry weight as Aroclor 1242 and 1254) in flow-through sea-water systems for 40 days to allow organisms to attain steady state concentrations. In Phase II the dietary fraction of PCB accumulation was determined by selectively feeding exposed and control groups of fish polychaetes having a known PCB body burden. In addition the effect of direct sediment contact on PCB accumulation by L. xanthurus was investigated. Results demonstrate that contaminated sediments can serve as a source of PCBs for uptake and trophic transfer in marine systems. Fish exposed to PCB-contaminated sediments and fed a daily diet of polychaetes from the same sediment accumulated more than twice the PCB whole-body residues than fish exposed to similar conditions but fed uncontaminated polychaetes. The dietary contribution of PCBs accounted for 53% of the total body burden measured in fish fed for 20 days, and this percentage appeared to be increasing. Results also indicate that fish isolated from direct contact with PCB-contaminated sediment do not significantly (P ≤ 0.05) accumulate PCB residues when compared with fish allowed contact with sediment.     

Estrogenic followed by anti-estrogenic effects of PCBs exposure in juvenil fish (Spaurus aurata)

Vitellogenin (Vtg) is a phospho-lipo-glycoprotein produced by oviparous animals in response to estrogen receptor (ER) binding. The presence of Vtg in juvenile and male fish liver and plasma has been used as biomarker to evaluate levels of environmental contaminants as dioxin and PCBs. Interaction of dioxins and PCBs with aryl hydrocarbon receptor (AhR) may affect reproduction by recruitment of estrogen receptor α (ERα). The aim of this study was to investigate the effects of PCB-126, a co-planar PCB prototypical AhR agonist, and of PCB-153, a non-coplanar PCB lacking dioxine-like activity, on Vtg expression in young fish (Spaurus aurata) after a 12 or 24 h exposure to PCBs as well as 48 h following PCBs removal. Vtg expression was evaluated by immunohistochemistry and by Western-blot analysis. Our results showed an increased Vtg expression following PCBs administration, with a maximum level after 12 h of exposure to either PCB-126, PCB-153 or a mixture of both PCBs. Following this estrogenic activity, an anti-estrogenic activity was detected after 24 h of incubation with PCB-126 (alone or mixed with PCB-153), suggested by a decrease in Vtg expression likely through AhR, as a consequence of a hypothetic defence mechanism to endogenous or exogenous ligands.     

Biological monitoring of indoor-exposure to dioxin-like and non-dioxin-like polychlorinated biphenyls (PCB) in a public building

The release of PCBs from sealant material in public buildings and the resulting indoor air levels have raised growing concerns about possible human health effects connected with this exposure. Ambient monitoring of PCBs in a public building has revealed a contamination with the more volatile lower chlorinated PCB 28, PCB 52 and PCB 101. This gave reason for a large biological monitoring study in order to examine the internal exposure to PCBs in persons working in that building. Blood samples from 209 persons employed in the PCB-contaminated building were drawn. 98 persons matched for age and gender working in non-contaminated buildings served as control group. Plasma samples were analysed for the six indicator PCBs (PCB 28, 52, 101, 138, 153, 180) and 12 dioxin-like PCBs using GC/MS (LOD: 0.01 μg/L). Significant differences between both collectives were only found for the plasma levels of the lower chlorinated PCB 28, PCB 52 and PCB 101 and for the dioxin-like congeners PCB 105 and PCB 118, which are due to inhalative exposure to these congeners via indoor air. Median plasma levels of PCB 28, PCB 52 and PCB 101 in the employees of the contaminated building were 0.087 μg/L, 0.024 μg/L and 0.012 μg/L, respectively. The concentrations of the higher chlorinated PCBs and all other dioxin-like congeners investigated were within the normal range of the general population. There was no relationship between indoor air measurements and internal exposure of the employees in the corresponding office, but estimated lifetime exposure of the employees turned out to be a significant factor for plasma levels of PCB 28. Our biomonitoring results served as a basis for individual risk communication and successful risk management.     

Effects of aqueous exposure to polychlorinated biphenyls (Aroclor 1254) on physiology and behavior of smolt development of Atlantic salmon

Polychlorinated biphenyls (PCBs) are a widespread aquatic contaminant and are present in both wild and hatchery raised Atlantic salmon, Salmo salar. The possible sub-lethal alterations in smolt physiology and behavior due to PCB exposure of salmon have not been widely examined. In this study, we examined the effects of the PCB mixture Aroclor 1254 on survival and smolt development of Atlantic salmon. In separate experiments, fish were exposed as yolk-sac larvae or as juveniles just prior to the parr-smolt transformation in April to 1 microgl(-1) (PCB-1) or 10 microgl(-1) (PCB-10) aqueous Aroclor 1254 (A1254), or vehicle for 21 days. After exposure, yolk-sac larvae were reared at ambient conditions for 1 year, until the peak of smolting the following May. Juveniles were sampled immediately after exposure. Both groups were assessed for behavioral, osmoregulatory, and endocrine disruption of smolt development at the peak of smolting. PCB-1 and PCB-10 treated yolk-sac larvae exhibited significant increases in the rate of opercular movement after 14 and 21 days of exposure. At the peak of smolting, prior exposure as yolk-sac larvae to PCB-1 did not affect behavior, while PCB-10 dramatically decreased volitional preference for seawater. Neither concentration of A1254 had long-term effects on the osmoregulatory or endocrine parameters measured in animals exposed as yolk-sac larvae. Juvenile fish exposed to PCB-1 or PCB-10 during smolting exhibited a dose-dependent reduction in preference for seawater. Fish treated with the higher dose of A1254 also exhibited a 50% decrease in gill Na(+),K(+)-ATPase activity and a 10% decrease in plasma chloride levels in freshwater. In addition, plasma triiodothyronine was reduced 35-50% and plasma cortisol 58% in response to exposure to either concentration; whereas plasma thyroxine, growth hormone, and insulin-like growth factor I levels were unaffected. These results indicate that the effects of exposure to A1254 may vary according to developmental stage. Exposure to A1254 in the freshwater environment can inhibit preparatory adaptations that occur during smolting, thereby reducing marine survival and sustainability of salmon populations.     

Relationship between PCBs in blood and D-glucaric acid in urine

The polychlorinated biphenyls (PCBs) have been demonstrated to be inducers of hepatic microsomal enzymes and some of their effects such as hormonal imbalance, and alteration of lipid and porphyrin metabolism could be ascribed to this mechanism. For this reason, the urinary excretion of D-glucaric acid (DGA), an indirect indicator of enzymatic induction, was suggested as a biological marker of effect following exposure to PCBs. The aim of the present study was to investigate whether any inductive effects resulting from exposure to these compounds through ingestion of contaminated food could be detected early by measuring urinary DGA (U-DGA). U-DGA was measured in 73 subjects exposed to PCBs due to ingestion of PCB-contaminated food and levels ranged from 1.7 to 12.4 mmol/mol creatinine, with a mean value of 5.96 mmol/mol creatinine. These values were higher than those usually found in the general population. Sex and smoking habits did not affect U-DGA excretion, while age and alcohol intake were significantly correlated with U-DGA excretion, a finding in agreement with the results of other investigations. Neither total PCB blood concentration nor PCB chlorine content was significantly correlated with U-DGA excretion, and only the PCB 138 congener was weakly correlated with U-DGA levels. The results indicate that, for exposure to PCB resulting in blood concentrations up to 394 microg/l, no statistically significant effect of these persistent organochlorine compounds on human enzyme induction could be demonstrated, as measured by DGA urinary excretion.     

The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats

Polychlorinated biphenyls (PCBs) are ubiquitious lipophilic environmental pollutants. Some of the PCB congeners and mixtures of congeners have tumor promoting activity in rat liver. The mechanism of their activity is not fully understood and is likely to be multifactorial. The aim of this study was to investigate if the resident liver macrophages, Kupffer cells, are important in the promoting activity of PCBs. The hypothesis of this study was that the inhibition of Kupffer cell activity would inhibit hepatic tumor promotion by PCBs in rats. To test our hypothesis, we studied the effects of Kupffer cell inhibition by dietary glycine (an inhibitor of Kupffer cell secretory activity) in a rat two-stage hepatocarcinogenesis model using 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153, a non-dioxin-like PCB) or 3,3',4,4'-tetrachlorobiphenyl (PCB-77, a dioxin-like PCB) as promoters. Diethylnitrosamine (DEN, 150 mg/kg) was administered to female Sprague-Dawley rats, which were then placed on an unrefined diet containing 5% glycine (or casein as nitrogen control) starting two weeks after DEN administration. On the third day after starting the diets, rats received PCB-77 (300 micromol/kg), PCB-153 (300 micromol/kg), or corn oil by i.p. injection. The rats received a total of 4 PCB injections, administered every 14 days. The rats were euthanized on the 10th day after the last PCB injection, and the formation of altered hepatic foci expressing placental glutathione S-transferase (PGST) and the rate of DNA synthesis in these foci and in the normal liver tissue were determined. Glycine did not significantly affect foci number or volume. PCB-153 did not significantly increase the focal volume, but increased the number of foci per liver, but only in the rats not fed glycine; PCB-77 increased both the foci number and their volume in both glycine-fed and control rats. Glycine did not alter the PCB content of the liver, but did increase the activity of 7-benzyloxyresorufin O-dealkylase (BROD) in liver microsomes from PCB-153 treated rats. However, glycine did not affect the induction of ethoxyresorufin O-dealkylase activity by PCB-77 in liver microsomes. Glycine diminished hepatocyte proliferation in PGST-positive foci, but not in normal tissue. Overall these results do not support the hypothesis that dietary glycine inhibits the promoting activities of PCBs. The observations that PCB-153 increased the number of foci per liver in control rats but not glycine-fed rats and that dietary glycine reduced cell proliferation in PGST-positive foci, however, do not allow us to completely rule out a role for dietary glycine. But the data overall indicate that Kupffer cells likely do not contribute to the tumor promoting activities of PCB-77 and PCB-153.     

Exposure of the population of the Slovak Republic to dietary polychlorinated biphenyls.

The aim of this paper has been to assess the exposure of the Slovak Republic population to polychlorinated biphenyls from food within 1994-2004. A total of 61167 samples of food of animal origin, including fats, were analyzed for the content of six PCB congeners (the sum of: PCB-28, PCB-52, PCB-101, PCB-138, PCB-153 and PCB-180); the commodities were divided into 48 basic groups. The exposure dose values based on actual and model consumption were calculated for an average inhabitant as well as for children of various age groups, and compared with the Tolerable Daily Intake value (TDI; 0.4 microg kg(-1) body weight per day). Knowledge and experience from a variety of projects running since 1991, as well as the database of food contaminants of the Centre for Evaluation of Contaminant Occurrence established at the Food Research Institute were utilized. The results of the evaluation suggested, that during the period of observation, the exposure of the Slovak Republic population to PCBs was relatively low. Taking actual consumption and mean findings as the basis, the daily exposure doses of PCBs ranged between 3.1% and 6.5% TDI, the corresponding figures for median value and the 95th percentile being between 1.4% and 4.0%, and between 7.5% and 20.0%, respectively.     

Altered protein expressions in chronic PCB-153-induced human liver (HepG2) cells

Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxic, endocrine disruption and reproductive abnormalities, including cancers. Chronic exposure to environmentally hazardous chemicals like PCBs is of great concern to human health. It has been reported earlier that apoptotic proteins change in rats under chronic PCB treatment. It is of importance to determine if chronically exposed human cells develop a different protein expression. In the present study, the authors chronically exposed metabolically competent human liver (HepG2) cells at 50 to 100 microM to examine the role of the well-known environmentally hazardous pollutant non-coplanar 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) to study cell death. After 12 weeks of exposure these cells showed significant changes in apoptotic death in subsequent trypan blue growth assay, fluorescence microscopy, DNA fragmentation, and immunoblotting studies. Interestingly, chronically exposed cells showed marked differences in apoptotic and/or death-related proteins (e.g., Bcl2, Bak, and the pro and active forms of caspase-9, which were up-regulated), in contrast to acutely exposed (i.e., 48-h PCB-153 exposed) cells, which maintained linear growth despite repeated exposures. Similarly, tumor suppressor protein p53, proto-oncogene c-myc, and cell cycle regulator protein p21 were also up-regulated compared to nonchronically exposed HepG2 Cells. The results indicated that PCB-153-induced chronic exposure significantly altered different apoptotic (e.g., Bcl2, Bak, caspase-3) and tumor suppressor (e.g., p21, p53, and c-myc) proteins in the cellular model. These results suggest that chronic exposure to PCB-153 can induce cell survival by altering several apoptotic and tumor suppressor proteins.     

Vitamin C intervention may lower the levels of persistent organic pollutants in blood of healthy women – A pilot study

Emerging evidence suggests that exposure to endocrine-disrupting chemicals including persistent organic pollutants (POPs) such as organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) has a long term impact on human health. The goal of this pilot study was to test whether antioxidant intervention by vitamin C supplementation may be a remedial approach to decrease body burden of POPs in humans. Using solid phase extraction coupled with a triple quadrupole mass spectrometer and a gas chromatography high resolution mass spectrometry, we measured 18 PCBs, 7 OCPs, and 5 PBDEs in the blood of 15 healthy California women (8 were obese/overweight and 7 had normal weight) before and after 2 months of vitamin C supplementation (1000 mg/day). We observed higher PBDE levels than PCBs and OCPs, but only PCB and OCP levels were strongly and positively correlated with participant's BMI and age. We also found statistically significant decreases in 6 PCBs (PCB-74, PCB-118, PCB-138, PCB-153, PCB-180, and PCB-187), and 2 OCPs (4,4′-DDE, and 4,4′-DDT), but not PBDEs after vitamin C supplementation. Pending confirmation of this pilot finding in a larger study of both sexes, vitamin C intervention may have important public health implications in protecting health by reducing body burdens of POPs.     

Congener-specific polychlorinated biphenyl-induced cell death in human kidney cells in vitro: potential role of caspase

Polychlorinated biphenyls (PCBs) are among the most widespread and persistent pollutants in the global environment. Coplanar and noncoplanar PCBs have been shown to cause congener-specific apoptosis mediated neurotoxicity in rats. Very few, if any, such studies have been reported on human renal cell toxicity. The authors report here caspase-dependent or caspase-independent renal toxicity, as measured by apoptotic death induced by PCBs, depending on the planarity of congeners PCB-77 (coplanar) and PCB-153 (noncoplanar) in human kidney cells (HK2) in vitro. The authors have combined morphological and biological techniques to discover the relevance of apoptosis in renal proximal tubule cell death induced by these two PCB congeners. Treatment with both PCB congeners caused accelerated apoptosis in a time- and concentration-dependent manner. Based on our findings using human kidney (HK2) cells, there was more apoptosis-mediated loss of cell viability by non-ortho-substituted PCB-77 when compared to PCB-153. A significant increase of caspase-3 expression through immunoblot studies showed the involvement of apoptosis by PCB-77 compared to none by PCB-153. The broad-spectrum caspase inhibitor z-VAD-fmk showed increased cell death when treated by PCB-153, but not by PCB-77, confirming that caspase inhibitor induced a switch in the mode of cell death. It is reasonable to assume that apoptotic cell death in the renal proximal tubule cells treated by PCBs may have both caspase-dependent and caspase-independent pathways.     

Effects of acute exposure to PCBs 126 and 153 on anterior pituitary and thyroid hormones and FSH isoforms in adult Sprague Dawley male rats.

3,3'4,4',5-Pentachlorobiphenyl (PCB 126) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) were administered to adult male rats in order to identify sensitive indicators of endocrine disruption. We tested the hypothesis that PCB exposure modifies follicle-stimulating hormone (FSH) pituitary isoforms, as well as the pituitary and serum concentrations of FSH, luteinizing hormone (LH), growth hormone, prolactin, and thyroid-stimulating hormone (TSH). Effects on serum levels of thyroxine (T4) and testosterone (T), and prostate androgen receptor content, were also tested. In one experiment, 5 groups of 8 rats each received two i.p. injections, one day apart, of either corn oil or 6.25, 25, 100 or 400 micrograms/kg/day of PCB 126. Decreases (p < 0.05) in the serum concentrations of T4 and LH started at doses of 25 and 100 micrograms/kg/day, respectively. Serum FSH concentrations were reduced (p = 0.07) in the highest dose group. In contrast, pituitary content of FSH and LH increased with PCB-126 doses (p = 0.004, p = 0.002, respectively). Despite changes in reproductive hormones, PCB-126 had no effect on the androgen receptor content of the prostate. The effect of PCB-126 was tested in the hemicastrated rat, and suggested adverse effects on testosterone secretion. To test the effects of PCB exposure on FSH pituitary isoforms, 4 groups of 10 male rats received two i.p. injections, one day apart, of either corn oil, PCB 153 (25 mg/kg/day), estradiol-17 beta (E2; 20 micrograms/kg/day), or PCB 126 (0.1 mg/kg/day). Serum T4 levels were higher (p < 0.01) in the E2 and PCB 153 groups, and slightly reduced in the PCB 126-treated groups, compared to controls. Simultaneous purification of pituitary FSH and TSH isoforms was performed by HPLC, using two chromatofocusing columns in series. In contrast to TSH isoforms, the distribution of FSH isoforms over the chromatography run differed slightly between treatment groups; the amounts of FSH isoform eluted during the pH gradient were lower (p < 0.05) in E2 and PCB 153-treated rats than in control or PCB 126-treated rats. The similarity between the effects of E2 and PCB 153 on T4 and FSH isoforms supports the contention that PCB 153 possesses estrogenic properties. Serum LH and T4 concentrations were the most sensitive and practical endocrine indicators of PCBs 126 and 153 exposure in male rats.     

Transport and cellular uptake of polychlorinated biphenyls (PCBs)--I. Association of individual PCB isomers and congeners with plasma lipoproteins and proteins in the pigeon

Polychlorinated biphenyls (PCBs) are abundant and persistent pollutants in the ecosystem. Commercial mixtures (e.g. Aroclor 1254) can contain up to 80 different isomers and congeners, many of which accumulate in biological systems by the ingestion of PCB-contaminated lipid components of food chains. PCBs are lipophilic and lipid-rich lipoproteins provide an excellent system to transport PCBs to tissues. We report here the distribution of PCBs between plasma fractions in the pigeon. Twenty-four hours after injection, [14C]4-monochlorobiphenyl and [14C]2,2',5,5'-tetrachlorobiphenyl were associated with the protein-rich HDL fraction and the lipoprotein-poor fraction (predominantly albumin), rather than with the lipid-rich VLDL and LDL fractions. Five days after injection with the commercial PCB mixture Aroclor 1254, there was a distinctive distribution between the plasma fractions of the 41 congeners detected. Avian species have a poorly developed lymphatic system and dietary lipids are secreted into the portal vein. To emphasize this route of entry, the lipoprotein particles formed are termed portomicrons rather than chylomicrons. The most striking result was that the lipid-rich portomicron and the VLDL fraction was associated almost exclusively with only one congener (2,2',4,4'5,5'-hexachlorobiphenyl), whereas the other isomers and congeners were distributed amongst the LDL, HDL and the lipoprotein-poor (predominantly albumin) fractions. Thirteen of the congeners detected accounted for 74, 53 and 54%, respectively, of the total amount of PCBs in the LDL, HDL and lipoprotein-poor protein fractions. Five congeners that are highly toxic were enriched in the latter fraction. The distribution of PCBs is more complex than can be explained solely by their solubility in the lipid components of plasma fractions, and may suggest a complex association with apolipoproteins and plasma proteins that are important in transporting PCB to tissues. The identification of individual PCBs in lipoprotein fraction provides evidence for their role in the transport of lipophilic xenobiotics in blood and it is suggested that PCBs associated with lipoproteins are taken up by cells as lipoprotein-PCB complexes.     

Hypertrophic Foci of Pancreatic Acinar Cells in Rats

Abstract

Polychlorinated biphenyls (PCBs) are a mixture of 209 different chlorinated biphenyl congeners (forms) of which 36 are environmentally relevant. PCBs are lipid (fat)-soluble, stable compounds. PCBs may be contaminated with more highly toxic polychlorinated dibenzofurans (PCDFs). Some PCDFs were primarily responsible for the two poisoning outbreaks — Yusho and Yu-Cheng.

Based on the reports on workers and the general population, no clear and convincing evidence that PCB exposures were casually associated with adverse health effects was advanced; this included cancer for a wide range of body burdens and exposures for serum PCB concentrations >1000 ppb (µ.g/1) and adipose PCB levels >400 ppm (mg/kg). No meaningful reproductive problems have been identified in female capacitor workers. In the opinion of the review author, the available evidence for cancer and for reproductive effects is inconclusive.

Adverse neurobehavioral effects in infants and young children have been reported in a study of women in the general population and a study of fish eaters and their offspring. The adverse effects observed in the two studies were not the same; the exposure assessments in both studies are not well defined and have many uncertainties.

Subhuman primates appear to be more sensitive to reproductive and other adverse effects of PCBs than humans. Obvious external clinical signs are observed in the offspring of subhuman primates at dosage levels below those experienced by female capacitor workers and members of the general population prior to the control of PCBs.     

In utero exposure to low-dose 2,3',4,4',5-pentachlorobiphenyl (PCB 118) impairs male fertility and alters neurobehavior in rat offspring

Neurobehavior (motor activity and developmental reflexes) and male reproductive parameters were evaluated in rat offspring after in utero exposure to a low dose of PCB 118 comparable to human exposure levels. Sprague-Dawley dams were treated on gestation day 6 by gavage with a single dose of 375 microg PCB 118/kg body weight or peanut oil (control). The dose was calculated to be approximately 100-fold higher than that found in human breast milk. Postnatal reflexes, motor activity and male reproductive performance were evaluated in rat offspring after exposure to PCB 118. Evaluation of locomotor activity for five consecutive days during puberty (PND 70-74) revealed hyperactivity in offspring from PCB 118-exposed dams. In adult males (PND 170), clear effects on reproductive organs were observed in PCB-exposed animals which had smaller testes, epididymides and seminal vesicles (absolute and relative weights). Decreases in sperm and spermatid numbers and impairment of daily sperm production were also observed. Our results clearly demonstrate that low-dose exposure to PCB 118 alters neurobehavior and impairs adult male fertility in offspring. This is in contrast to the reported increases in sperm production and testis weight in rat after high dose PCB exposures. PCBs appear to possess variable dose-related effects and therefore low-dose studies are important to obtain a complete picture for human risk assessment.     

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.