The Duisburg birth cohort study: influence of the prenatal exposure to PCDD/Fs and dioxin-like PCBs on thyroid hormone status in newborns and neurodevelopment of infants until the age of 24 months

Prenatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) can affect neurobehavioral development of infants and children. This effect may be mediated through disruption of thyroid hormone homeostasis. However, epidemiological studies reveal no consistent influence of PCDD/Fs and PCBs on thyroid status and neurodevelopment at environmental background levels. The effects may resolve with time of further decreasing exposure to these compounds. The aim of this study was to find out if there are still effects related to prenatal PCDD/F and PCB observable at the meanwhile decreased levels of exposure by using the same methods which have been applied in similar studies during the last 10 years in Europe. The birth cohort study was initiated in the year 2000 in the industrialized city of Duisburg, Germany. 232 healthy mother-infant pairs were recruited between 2000 and 2002. Dioxins, dioxin-like PCBs and six indicator PCBs were analyzed in maternal blood during pregnancy and in maternal milk following extraction and sample clean-up by HRGC/HRMS. Thyroid stimulating hormone (TSH), total thyroxine (T4), total triiodothyronine (T3), free thyroxine (FT4) and free triiodothyronine (FT3) were measured in serum samples of the pregnant women and in cord serum samples by chemiluminescent immunometric assay. Neurological examinations were performed at ages 2 weeks and 18 months using the neurological optimality score (NOS), mental and motor development were assessed using the Bayley Scales of Infant Development (BSID) at ages 12 and 24 months. Multiple linear regression analysis was used to describe the association of PCDD/F and PCB in maternal blood or milk with the outcome measurements after adjustment for confounding. Blood levels (n=182) of WHO 2005 toxic equivalents (TEQ) (PCDD/F+PCB) were in the range of 3.8-58.4 pg/glipid base (median: 19.3 pg/glipid base). The corresponding data for human milk (n=149) were 2.6-52.4 pg/glipid base (median: 19.7 pg/glipid base). Multiple regression analysis showed no decrease of thyroid hormones related to WHO 2005 TEQ in blood and milk of mothers and their newborns. Furthermore, no associations between exposure and neurological and developmental measures were observed. This study supports the view that the current decreased exposure to PCDD/Fs and PCBs does not impair thyroid function of newborns and neurodevelopment of infants until the age of 24 months.     

Polychlorinated Biphenyls in the Plasma and Preen Oil of Black-Footed Albatross (Diomedea nigripes) Chicks and Adults on Midway Atoll,North Pacific Ocean

Polychlorinated biphenyls (PCBs) are ubiquitous in the environment. Midway Atoll, located in the North Pacific Ocean, was occupied by the military during and after World War II. However, Midway Atoll has become a national wildlife refuge and home to many different seabirds today, including the black-footed albatross (Diomedea nigripes) (BFAL). The profiles and toxic equivalents (TEQ) of PCB congeners in the plasma and preen oil of BFAL chicks and adults were determined in this study. The concentrations of the total PCBs in the plasma samples of chicks and adults collected in Midway Atoll ranged from 2.3 to 223.8 (mean 80.1) and 22.8 to 504.5 (mean 158.6) ng g^-1 (wet weight, ww), respectively. The TEQs ranged from 0.2 to 0.6 (mean 0.4) and 0.4 to 1.6 (mean 0.9) pg g^-1 ww, respectively, in the plasma samples of chicks and adults from Midway Atoll. The major congeners in the plasma samples of chicks and adults included PCBs 31, 87, 97, 99, 118, 138, 153, and 180, accounting for 70% of the total PCBs. The concentrations of the total PCBs in the adult preen oil samples ranged from 1693 to 39404 (mean 10122) ng g^-1 (ww), of which 97% were PCBs 105, 118, 128, 138, 153, 161, 172, and 183.     

Time dependent and cell-specific action of polychlorinated biphenyls (PCB 153 and PCB 126) on steroid secretion by porcine theca and granulosa cells in mono- and co-culture.

To characterize PCB action on follicular cell steroidogenesis two PCB congeners were selected as model substances. PCB 126 because of its dioxin-like configuration and high toxicity and PCB 153 because it is one of the most commonly detected PCB congeners in breast milk. The direct effect of PCBs was investigated using a culture system of porcine theca and granulosa cells collected from porcine preovulatory follicles. Granulosa and theca cells were cultured in M199 medium supplemented with 1, 10 or 100 pg/ml of PCB 126 or 1, 10 and 100 ng/ml of PCB 153. The media were changed after 48, 96 and 144 h and frozen until further estradiol (E2) analysis. Additionally, progesterone (P4) was measured in the granulosa cells culture medium and testosterone (T) in theca cells culture medium. Decrease of testosterone concentration in the theca cells culture medium was found after 96 and 144 hours in culture by both investigated PCB congeners. A decrease in E2 concentration was found after exposure to PCB 153. These findings suggest different actions of two congeners on the steroid synthesis in theca cells. The lack of an increase in E2 secretion after the exposure to PCB 126 could be due to depletion of androgen precursor. In granulosa cell culture PCB153 decreased E2 secretion and increased P4 secretion suggesting luteinization and disruption of aromatization process. PCB 126 in a doses from 1 to 10 pg had no effect on granulosa cells steroidogenesis. However, the highest dose (100 pg) increased concentration of both E2 and P4. This observation suggest that PCB 126 in a pharmacological doses may affect cell membrane permeability, thereby increasing steroid outflow into the medium. These results suggest time dependent and cell-specific differences in PCB 153 and 126 action on follicular cells steroidogenesis. Further studies are required to elucidate the mechanism of PCBs action on ovarian steroidogenesis.     

Distribution and Toxicity Risks of PCBs in the Tidal Flat Ecosystem Near the 37th PCBs Sealed Site on the Coast of Zhejiang Province,China

This study investigated the dioxin-like (DL) PCB concentration and congener distributions in water, sediment, and Boleophthalmus pectinirostris samples collected from a beach near the 37th PCBs sealed site (the hazardous waste storage site was sealed by Zhejiang Province Environmental Monitoring Center) of Zhejiang Province, China, so as to evaluate the harmful effects of PCBs waste sealed sites on the surrounding environment. The results showed that DL-PCBs were in all samples. For all samples, the detection ratio of the mono-ortho congener PCB118 and the non-ortho congener PCB81 reached 100%, and both of their contents correlated well with the total DL-PCBs contents. Levels of low-chloride congeners were higher in environmental samples, while the enrichment of the high-chloride congeners was higher in fish. The content of PCBs in B. pectinirostris was highly related to the sediment environment, thus B. pectinirostris could well indicate environmental PCBs pollution. Considering both of the PCBs content and toxic analysis, even after 4 years of being excavated and cleaned, water, sediment, and fish samples were still at a certain degree of toxicity risks. Some areas were revealed to have a high toxicity risk, suggesting this PCBs sealed site still posed toxicity risks to the surrounding tidal flat ecosystem and might potentially endanger animals and human health.     

Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6/J mice

BackgroundPolychlorinated biphenyls (PCBs) are persistent environmental pollutants that are detectable in the serum of all American adults. Amongst PCB congeners, PCB 153 has the highest serum level. PCBs have been dose-dependently associated with obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in epidemiological studies.ObjectiveThe purpose of this study is to determine mechanisms by which PCB 153 worsens diet-induced obesity and NAFLD in male mice fed a high-fat diet (HFD).MethodsMale C57BL6/J mice were fed either control or 42% milk fat diet for 12 weeks with or without PCB 153 coexposure (50 mg/kg ip ×4). Glucose tolerance test was performed, and plasma and tissues were obtained at necropsy for measurements of adipocytokine levels, histology and gene expression.ResultsIn control diet-fed mice, addition of PCB 153 had minimal effects on any of the measured parameters. However, PCB 153 treatment in high-fat-fed mice was associated with increased visceral adiposity, hepatic steatosis and plasma adipokines including adiponectin, leptin, resistin and plasminogen activator inhibitor-1 levels. Likewise, coexposure reduced expression of hepatic genes implicated in β-oxidation while increasing the expression of genes associated with lipid biosynthesis. Regardless of diet, PCB 153 had no effect on insulin resistance or tumor necrosis factor alpha levels.ConclusionPCB 153 is an obesogen that exacerbates hepatic steatosis, alters adipocytokines and disrupts normal hepatic lipid metabolism when administered with HFD but not control diet. Because all US adults have been exposed to PCB 153, this particular nutrient–toxicant interaction potentially impacts human obesity/NAFLD.     

Prenatal Exposure to a Polychlorinated Biphenyl (PCB) Congener Influences Fixation Duration on Biological Motion at 4-Months-Old: A Preliminary Study

Adverse effects of prenatal exposure to polychlorinated biphenyl (PCB) congeners on postnatal brain development have been reported in a number of previous studies. However, few studies have examined the effects of prenatal PCB exposure on early social development. The present study sought to increase understanding of the neurotoxicity of PCBs by examining the relationship between PCB congener concentrations in umbilical cord blood and fixation patterns when observing upright and inverted biological motion (BM) at four-months after birth. The development of the ability to recognize BM stimuli is considered a hallmark of socio-cognitive development. The results revealed a link between dioxin-like PCB #118 concentration and fixation pattern. Specifically, four-month-olds with a low-level of prenatal exposure to PCB #118 exhibited a preference for the upright BM over inverted BM, whereas those with a relatively high-level of exposure did not. This finding supports the proposal that prenatal PCB exposure impairs the development of social functioning, and indicates the importance of congener-specific analysis in the risk analysis of the adverse effects of PCB exposure on the brain development.     

Residues of polychlorinated biphenyls in breast milk of women non-occupationally exposed to PCBs

Samples of breast milk were collected from 27 women and examined for residues of polychlorinated biphenyls (PCBs) using gas-liquid chromatography. A questionnaire was used to obtain information on environmental factors relevant to the women's exposure to PCBs. The levels of breast milk PCB residues were considered in relation to the women's medical history before and during pregnancy and to the health status of the infants. Despite the fact that the production and use of PCBs were banned in Czechoslovakia in 1982, all breast milk samples tested had detectable levels of PCBs, with the average value of 2,411 ng.g-1 milk fat (i.e., 22.8 ng.g-1 whole milk). In 25% of the women the PCB levels were higher than 2,500 ng.g-1 milk fat, which is considered a limit concentration for PCB in breast milk.     

Alteration of serotonin system by polychlorinated biphenyls exposure

Although commercial production of polychlorinated biphenyls (PCBs) was banned in 1979, PCBs continue to be an environmental and health concern due to their high bioaccumulation and slow degradation rates. In fact, PCBs are still present in our food supply (fish, meat, and dairy products). In laboratory animals, exposure to single PCB congener or to mixtures of different congeners induces a variety of physiological alterations. PCBs cross the placenta and even exposure at low level is harmful for the foetus by leading to neurodevelopment alterations. Serotonin system which regulates many physiological functions from platelet activation to high cerebral processes and neurodevelopment is one of the targets of PCBs toxicity. The effects of PCBs exposure on serotonin system have been investigated although to a lesser extent compared to its effect in other neurotransmitter systems. This review provides a summary of the results concerning the impact of PCBs exposure (in vitro and in vivo) on serotonin system. Further research is needed to correlate specific deficits with PCB-induced changes in the serotonin system.     

Effects of reproductive strategies on pollutant concentrations in pinnipeds: a meta‐analysis

In marine mammals such as pinnipeds (seals, sea lions and walruses), reproductive strategies reveal how species acquire, store and allocate energy to offspring. During lactation, females can allocate energy acquired from concurrent resources (income breeding); or utilize energy stored prior to reproduction (capital breeding). Mothers transfer a large proportion of energy to their pups via lipid rich milk, meaning that pollutants such as polychlorinated biphenyls (PCBs) and mercury (Hg) will also transfer, raising concern for negative health effects. To quantify the effect of reproductive strategy on maternal pollutant transfer in pinnipeds, we developed a proxy for income and capital breeding by focusing on the lactational component of reproduction, and arranged species along this gradient. We found a strong positive relationship between lipid content in milk and degree of capital breeding. We tested this gradient against maternal pollutant transfer expressed as a concentration ratio by meta‐analysis. In mother‐pup pairs, the concentration ratio of PCBs was one order of magnitude higher than for mercury. PCB concentrations in pups and juveniles were similar to adult females, but mercury was always lower in young offspring than in females. We found no effect of reproductive strategy between studies investigating mother‐pup pairs and non‐related females and juveniles (< 1 year old), however data were strongly biased towards capital breeders. Our results suggest that either: 1) reproductive strategy does not affect pollutant bioaccumulation; or 2) a lack of income breeder data prevents us from testing the overall effect of reproductive strategy on maternal pollutant transfer. The finding that PCB concentrations in juveniles are similar to females is of concern due to early life stage exposure. We recommend data collection from income breeding species such as the sea lions to elucidate whether reproductive strategy, and potentially other life history traits, has an overall effect on maternal pollutant transfer.     

Reconstituted human breast milk PCBs as potent inducers of aryl hydrocarbon hydroxylase

The major polychlorinated biphenyl (PCB) components identified in human breast milk have been synthesized and a reconstituted breast milk PCB mixture representing the average levels determined in the Osaka Prefecture in Japan has been prepared. The dose effecting the half-maximal (ED₅₀) induction of rat hepatic microsomal aryl hydrocarbon hydroxylase (AHH) for the reconstituted breast milk PCBs (ED₅₀ ～12 μmol·kg^?1) was approximately seven times less than the ED₅₀ for the commercial PCB mixture, Kanechlor 500. The increased biological potency of the former mixture reflects the preferential bioconcentration of the toxic PCB congeners, 2,3,3′,4,4′-penta-, 2,3′,4,4′,5-penta- and 2,3,3′,4,4′,5-hexachlorobiphenyl.     

Relationship between paired cord blood and milk POPs levels as a tool for assessing perinatal exposure,a pilot study

The long-term health threats posed to humans exposed to pollutants acting as endocrine disruptors (EDs) is yet to be quantified. There is insufficient knowledge about the sources and magnitude of exposure to selected polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) during the most sensitive period of fetal development, suggesting the need for a study. Organochlorine pesticides, classified as being persistent organic pollutants (POPs) and potential EDs, were also included in this analysis. Xenobiotics were measured in paired fetal cord blood and maternal breast milk samples. There were no significant differences in the concentrations of PCB-101, PBDE-47, and PBDE-99 between maternal milk and cord blood according to the Wilcoxon test, and the Spearman tests demonstrated significant correlations in β-HCH, γ-HCH, p,p'-DDE, and PCB-118 between maternal milk and cord blood from the same subjects. All others tested (HCB, β-HCH, γ-HCH, p,p'-DDE, p,p'-DDD, p,p'-DDT, PCB-101, PCB-138, PCB-153, PCB-170, PCB-180, PBDE-153) demonstrated significant differences in the same subject women with concentrations significantly higher in maternal milk than in cord blood. The presence of these compounds found in cord blood and maternal milk indicates that both are a source of perinatal exposure to these pollutants. This study opens up the opportunity for new research in estimating a prenatal exposure based on breast milk concentrations of organohalogen compounds.     

Response to stress of mussels (Mytilus edulis) exposed in Dutch tidal waters.

1. Mussels were exposed in the Dutch coastal zone and the Western Scheldt estuary. After six weeks of exposure, trace metals, PCBs and PAHs were measured in the soft tissue. 2. Tissue concentrations of contaminants are high in the Western Scheldt and intermediate near the Rhine outflow, except for the lower PCB congeners. 3. Results show that the survival in air is significantly lower at higher tissue concentrations, in particular of the lower PCB congeners. 4. The clearance rate is reduced at the highest tissue concentrations.     

Effects of polychlorinated biphenyls on cytochrome P450 induction in the chick embryo hepatocyte culture

The effects of pure synthetic polychlorinated biphenyl (PCB) congeners on the induction of cytochrome P450 and associated activities were examined in cultured chick embryo hepatocytes. Dose-response effects for the induction of total cytochrome P450 ethoxyresorufin-O-deethylase (EROD) activity, and benzphetamine demethylase (BPDM) activity were studied using 10 selected tetra- to hexachlorinated PCB congeners. These studies revealed that PCBs caused effects in the chick hepatocyte culture different from previously observed effects in rat liver. Based on their effects in chick hepatocytes, the PCBs could be categorized into two groups. The first group (consisting of 3,3',4,4'-PCB, 3,3',4,4',5-PCB, 3,3',4,4',5,5'-PCB, 2',3,3',4,5-PCB, 2,3,3',4,4',5'-PCB, and 2,3,4,4',5-PCB) induced total cytochrome P450 2.4- to 2.9-fold and EROD activity from 1-2 pmol/min/mg protein to 162-247. There was marked variation in potency, but all these congeners had a maximal inducing dose above which cytochrome P450 concentrations and EROD activities declined. BPDM activities were increased only slightly (1.2- to 1.6-fold) at the maximal cytochrome P450 inducing dose. The second group of congeners (consisting of 2,2',4,5,5'-PCB. 2,2',4,4',5,5'-PCB, and 2,2',3,4,4',6-PCB) induced total cytochrome P450 concentrations 4.0-fold and BPDM activities 2.2- to 2.6-fold with greatest activity occurring at the highest doses which could be added (10-50 microM). However, EROD activities were also increased by these congeners to 60-112 pmol/min/mg protein with declining activities seen at the highest PCB doses (i.e., resembling EROD induction patterns of the first group). The EROD induction patterns with these latter PCB congeners are noteworthy since these PCBs do not induce EROD activity in the rat. For both groups of PCB congeners, EROD induction was associated with increased accumulation of uroporphyrin in cultures exposed to exogenous 5-aminolevulinate. Studies investigating the reason for the depression of cytochrome P450 concentrations and/or EROD activities by high doses of the PCBs revealed that with the first group there was slightly decreased total protein synthesis, decreased total cell heme concentrations, and decreased accumulation of radiolabeled heme synthesized from 5-[14C]aminolevulinate. These changes might represent nonspecific toxic effects of the first group of PCBs. However, since these changes were not seen with the second group of PCBs, it is unlikely that either inhibition of heme synthesis or toxicity cause the depression of EROD activity with high PCB doses.     

Reproductive injury in English Sole (Pleuronectes vetulus) from the Hylebos Waterway, Commencement Bay, Washington

The effect of exposure to xenobiotic compounds on ovarian development was investigated in prespawning female English sole (Pleuronectes vetulus) from the Hylebos Waterway, an industrial site in Commencement Bay, WA, contaminated with aromatic hydrocarbons (AHs), polychlorinated biphenyls (PCBs)and other chlorinated compounds, including hexachlorobutadiene (HCBD) and hexachlorobenzene (HCB). Reference sole were collected from Colvos Passage, a nearby site with minimal sediment contaminant concentrations. English sole from theHylebos Waterway had significantly higher concentrations of fluorescent aromatic compounds (FACs) in bile, polycyclic aromatic compound-DNA adducts in liver, and dioxin-like and other selected PCB congeners in liver than sole from Colvos Passage. The Hylebos Waterway animals also showed significant alterations in their pattern of reproductive development when compared to Colvos Passage sole. Hylebos Waterway sole entered vitellogenesis at a nearlier age than Colvos Passage sole, with about 50%of fish below 5 years of age maturing in the Hylebos Waterway as compared to 20% of Colvos Passage sole in this age range, with corresponding increases in plasma estradiol concentrations and GSI in Hylebosfish. However, while the proportion of maturing Colvos Passage females increased with age to over70% for fish 5 years of age or greater, the proportion of maturing females in the Hylebos Waterway remained at about 50%. Moreover, plasma estradiol concentrations and gonadosomatic indices in these sole were depressed. Inhibited reproductive development and increased oocyte atresia in adult fish were correlated with elevated concentrations of FACs in bile. Enhanced growth, as well as exposure to both aromatic and chlorinated hydrocarbons, were associated with precocious maturation in sub adult Hylebos Waterway sole. This revised version was published online in July 2006 with corrections to the Cover Date.     

Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort

Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from chemical exposures. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood. The cord blood DNA methylome was profiled using Infinium HumanMethylation450 BeadChips. We determined the associations of CpG site changes with concentrations of MeHg, major PCBs, other organochlorine compounds [hexachlorobenzene (HCB), p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE) and p,p’-dichlorodiphenyltrichloroethane], and perfluoroalkyl substances. In a combined sex analysis, among the 16 chemicals studied, PCB congener 105 (CB-105) exposure was associated with the majority of differentially methylated CpG sites (214 out of a total of 250). In female-only analysis, only 73 CB-105 associated CpG sites were detected, 44 of which were mapped to genes in the ELAV1-associated cancer network. In males-only, methylation changes were seen for perfluorooctane sulfonate, HCB, and p,p’-DDE in 10,598, 1,238, and 1,473 CpG sites, respectively, 15% of which were enriched in cytobands of the X-chromosome associated with neurological disorders. In this multiple-pollutant and genome-wide study, we identified key epigenetic toxicants. The significant enrichment of specific X-chromosome sites in males implies potential sex-specific epigenome responses to prenatal chemical exposures.     

Thyroid hormone status of Atlantic croaker exposed to Aroclor 1254 and selected PCB congeners

Atlantic croaker (Micropogonias undulatus) were exposed to the polychlorinated biphenyl (PCB) mixture (Aroclor 1254) or one of three individual congeners (planar PCB 77 or ortho-substituted PCB 47 and PCB 153) in the diet for 30 days to investigate the effects of PCBs on circulating thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Aroclor 1254 (0.2 and 1.0 mg/kg body mass/day) decreased plasma T3 levels consistently, but the effects on T4 levels were inconsistent from year to year. Exposure to PCB 153 (0.1 and 1.0 mg/kg body mass/day) significantly lowered both T4 and T3, while PCB 47 at the same doses had no effect on thyroid hormone levels. The lower doses of PCB 77 (0.004, 0.01 and 0.02 mg/kg body mass/day) had no effect on T4 or T3, whereas the highest dose (0.1 mg/kg body mass/day) increased T4 levels significantly. The results of the present study demonstrate that exposure to PCBs at environmentally realistic concentrations can have profound effects on the thyroid status of Atlantic croaker. The ortho-substituted PCB 153 appears to contribute at least partially to the deleterious effects of Aroclor 1254 on thyroid status, whereas the planar PCB 77 at concentrations present in the mixture is unlikely to alter thyroid hormone levels.     

PCB disruption of the hypothalamus-pituitary-interrenal axis involves brain glucocorticoid receptor downregulation in anadromous Arctic charr

We examined whether brain glucocorticoid receptor (GR) modulation by polychlorinated biphenyls (PCBs) was involved in the abnormal cortisol response to stress seen in anadromous Arctic charr (Salvelinus alpinus). Fish treated with Aroclor 1254 (0, 1, 10, and 100 mg/kg body mass) were maintained for 5 mo without feeding in the winter to mimic their seasonal fasting cycle, whereas a fed group with 0 and 100 mg/kg Aroclor was maintained for comparison. Fasting elevated plasma cortisol levels and brain GR content but depressed heat shock protein 90 (hsp90) and interrenal cortisol production capacity. Exposure of fasted fish to Aroclor 1254 resulted in a dose-dependent increase in brain total PCB content. This accumulation in fish with high PCB dose was threefold higher in fasted fish compared with fed fish. PCBs depressed plasma cortisol levels but did not affect in vitro interrenal cortisol production capacity in fasted charr. At high PCB dose, the brain GR content was significantly lower in the fasted fish and this corresponded with a lower brain hsp70 and hsp90 content. The elevation of plasma cortisol levels and upregulation of brain GR content may be an important adaptation to extended fasting in anadromous Arctic charr, and this response was disrupted by PCBs. Taken together, the hypothalamus-pituitary-interrenal axis is a target for PCB impact during winter emaciation in anadromous Arctic charr.     

Identification and modification of biphenyl dioxygenase sequences that determine the specificity of polychlorinated biphenyl degradation.

The polychlorinated biphenyl (PCB) congener specificities and partial BphA sequences of biphenyl dioxygenase were determined for a set of PCB-degrading bacteria. The strains examined were categorized into two groups based on their ability to degrade 17 PCB congeners. Strains that degraded a broad range of PCBs but had relatively weak activity against di-para-substituted PCBs were designated as having an LB400-type specificity. Strains designated as having a KF707-type specificity degraded a much narrower range of PCBs but had strong activity against certain di-para-substituted congeners. BphA protein sequence comparisons between these two types of strains identified four regions (designated I, II, III, and IV) in which specific sequences were consistently associated with either broad or narrow PCB substrate specificity. The dramatic differences in substrate specificity between LB400 and KF707 appear to result primarily from a combination of mutations in regions III and IV. Altering these regions in the LB400 BphA subunit to correspond to those in the KF707 sequence produced a narrow substrate specificity very similar to that of KF707. Some individual mutations within region III alone were found to improve PCB degradative activity, especially for di-para-substituted congeners. However, the greatest improvements in activity resulted from multiple amino acid modifications in region III, suggesting that the effects of these mutations are cooperative. These results demonstrate the ability to significantly improve PCB oxidative activity through sequence modifications of biphenyl dioxygenase.     

Degradation of Polychlorinated Biphenyls by UV-Catalyzed Photolysis

Photolysis of five polychlorinated biphenyl (PCB) congeners [2,4,4′-trichlorobiphenyl (PCB 28), 2,2′,5,′5-tetrachlorobiphenyl (PCB 52), 2,2′,4,5,5′-pentachlorobiphenyl (PCB 101), 2,2′,4,4′,5,′5-hexachlorobiphenyl (PCB 153) and 2,2′,3,4,4′,5,′5-heptachlorobiphenyl (PCB 180)] individually and in combination were carried out in the solvents methanol, ethanol, and 2-propanol. The disappearance of parent congener generally increased with UV intensity. The solvents had significant or limited effect on the removal of PCBs depending on the congener used. Because 2-propanol was highly toxic and methoxylated products were formed when methanol was used, ethanol was selected as the optimum solvent. The results of photolysis of the PCB mixture showed that PCB 52 was formed and accumulated after 4 h of photolysis. The addition of sodium hydroxide increased the rate of photolysis of the PCB mixture. One hundred percent removal can be obtained of the PCB in mixture in 90 min under optimized conditions. Gas chromatography–mass spectrometry was used to determine the intermediates of the photolysis of PCBs under optimized conditions. For the PCB congeners and mixture studied, the major photolytic intermediates were less chlorinated congeners, and biphenyl was the major product with minor amounts of hydroxylated PCBs, ethylated, dimethylated, and methylated biphenyls. Biphenyl could be further degraded by a prolonged photolysis. Toxicity of the PCB mixture during photolysis was monitored by the Microtox^® test. It was found that the toxicity increased at the early stage of photolysis, and gradually decreased as the reaction proceeded. After 90 min, the EC₅₀ of the reaction mixture was similar to that of the untreated sample.     

Environmental Polychlorinated Biphenyl Exposure and Breast Cancer Risk: A Meta-Analysis of Observational Studies

Background

Association between polychlorinated biphenyl (PCB) exposure and breast cancer risk has been widely studied, but the results remain controversial. We performed a meta-analysis to evaluate the evidences from observational studies on PCB exposure and breast cancer risk.

Methods

Relevant studies with data on internal PCB dose were identified from PubMed, EMBASE, CBM and CNKI databases through November 2014. Multivariable-adjusted odds ratio (OR) with 95% confidence intervals (CIs) were applied to assess the association between PCB exposure and breast cancer risk. Heterogeneity test, sensitivity analysis, subgroup analysis and publication bias test were also performed. To further explore the association between specific groups of PCB congeners and breast cancer, we examined the PCB congeners classified, according to their structural, biological and pharmacokinetics properties, as group I (potentially estrogenic), group II (potentially anti-estrogenic and immunotoxic, dioxin-like), and group III (phenobarbital, CYP1A and CYP2B inducers, biologically persistent).

Results

Of 660 studies screened, 25 studies which met criteria were selected, involving a total of 12866 participants (6088 cases and 6778 controls) from eight countries. The results showed that the risk of breast cancer was associated with group II (OR = 1.23, 95% CI: 1.08–1.40) and group III (OR = 1.25, 95% CI: 1.09–1.43) PCBs, but not with group I (OR = 1.10, 95%CI: 0.97–1.24) PCBs or total PCB exposure (OR = 1.09, 95%CI: 0.97–1.22).

Conclusions

Our meta-analysis based on the selected studies found group II and group III PCB exposure might contribute to the risk of breast cancer. More studies in developing countries with higher PCB levels are needed, as well as studies to explore the relationships between mixtures of organochlorine compounds and breast cancer risk.