Coplanar Polychlorinated Biphenyls Research Articles

Dioxins (Polychlorinated Dibenzo-p-dioxins, Polychlorinated Dibenzofurans and Coplanar PCBs) in Human Milk

Dioxins (Polychlorinated Dibenzo-p-dioxins, Polychlorinated Dibenzofurans and Coplanar PCBs) in Human Milk

The Relationship Between Noncoplanar PCB-Induced Immunotoxicity and Hepatic CYP1A Induction in a Fish Model

Abundant literature exists demonstrating the immunomodulating effects of polychlorinated biphenyls (PCBs). To date, most of the research has focused on dioxin-like coplanar PCB congeners because of their high affinity for the aryl hydrocarbon receptor (AhR) and cytochrome P450-inducing capability. For this study, the impact of two structurally different PCB congeners on the immune responsiveness of bluegill sunfish (Lepomis macrochirus) was examined to evaluate the immunotoxic potential of each congener (as separate entities) and to relate effects on immune function with hepatic CYP1A induction. Fish received a single intraperitoneal injection of the: coplanar congener, PCB 126 (0.01 or 1.0 μg/g BW); noncoplanar PCB 153 (5.0 or 50.0 μg/g BW); or, the corn oil vehicle. PCB-induced effects on innate and cell-mediated immune parameters, and on hepatic CYP1A protein induction were evaluated in fish sacrificed 1, 3, 7, 14 or 21 days post-injection. In the absence of CYP1A induction, PCB 153 increased kidney phagocyte-mediated superoxide production 3 d post-injection, and at the highest dose suppressed B- and T-lymphocyte proliferation after 3 and 7 days, respectively. Treatment of fish with PCB 126 had no effect on oxyradical production, but altered B-lymphocyte proliferation after 1 day, also in the absence of CYP1A induction. Hepatic CYP1A was only induced in fish exposed to the highest PCB 126 dose; protein induction appeared at 3 d post-injection and persisted for up to 21 days. Taken together, these results demonstrate that exposure to different PCB congeners can alter immune function in the absence of CYP1A induction, suggesting that mechanisms other than the AhR pathway may play a role in PCB-induced immunotoxicity, particularly for the noncoplanar congeners.

Prenatal Exposure to Polychlorinated Biphenyls and Postnatal Growth: A Structural Analysis

Normal endocrine function in utero and early in childhood influences later height and weight attainment. Polychlorinated biphenyls (PCBs) are persistent environmental contaminants with suspected endocrine-disrupting properties. PCBs may mimic or inhibit hormone and endocrine processes based in part on their structural configuration, with non-ortho-substituted PCBs having a coplanar orientation and ortho-substituted PCBs becoming increasingly noncoplanar. Coplanar and noncoplanar PCBs have known differences in biologic effect. Animal studies link prenatal PCB exposure to adverse birth and early-life growth outcomes, but epidemiologic studies are conflicting. We examined whether prenatal exposure to PCBs, categorized by their degree of ortho-substitution, affected childhood height and weight attainment in 150 children (109 boys and 41 girls) with African-American mothers born at the Columbia-Presbyterian Hospital from 1959 through 1962. Stratifying by sex, we used regression models for repeated measures to investigate associations between maternal levels of PCBs and height and weight through 17 years of age. Maternal levels of ortho-substituted PCBs were associated with reduced weight through 17 years of age among girls but not among boys. Tri-ortho-substituted PCBs were marginally associated with increased height in boys. Although limited by sample size, our results suggest that prenatal exposure to PCBs may affect growth, especially in girls, and that ortho-substitution is an important determinant of its effect on growth.

Effect of PCB 126 on Hepatic Metabolism of Thyroxine and Perturbations in the Hypothalamic-Pituitary-Thyroid Axis in the Rat

The objective of this research was to examine the time- and dose- dependent disturbances in the hypothalamic-pituitary-thyroid (HPT) axis of adult male rats administered a potent coplanar (non-ortho) PCB, 3,3',4,4',5-pentachlorobiphenyl (PCB 126). Adult male Sprague-Dawley rats were administered a single oral bolus dose of 0, 7.5, 75, or 275 microg PCB 126/kg bw dissolved in corn oil. The rats were sacrificed periodically over 22 days. The 7.5-microg/kg dose induced hepatic ethoxyresorufin-O-deethylation EROD activity, but no changes were observed in hepatic uridine diphosphate glucuronyl transferases (UDPGTs) activity or serum TSH, T4, or fT4 concentrations. The two highest doses caused a modest decline in weight gain, induced hepatic EROD and UDPGT activities, increased serum TSH concentrations, and decreased serum T4 and fT4 concentrations. The amount of thyroxine glucuronide formed daily (pM/mg protein) increased linearly with the area-under-the-concentration-curve (AUCC) for PCB 126 in liver (microg/kg/day) and then slowed at the 275-microg/kg PCB 126 dose. Perturbations in the HPT axis were nonlinear with respect to PCB 126 dosing. As expected, an inverse relationship between the AUCC for serum T4 (microg/dl/day) and the AUCC for serum TSH (ng/dl/day) was observed; however, the relationship was highly nonlinear. These data support a mode of action for PCB 126 involving induction of hepatic UDPGTs by the aryl hydrocarbon receptor AhR. However, the dose-response characteristics of the HPT axis are nonlinear and complex, requiring sophisticated tools, such as PBPK models, to characterize dose response.

Apoptosis in bovine cumulus–oocyte complexes after exposure to polychlorinated biphenyl mixtures during in vitro maturation

Aroclor-1254 (A-1254) is a commercial mixture of coplanar (dioxin-like) and non-coplanar (non dioxin-like) polychlorinated biphenyls (PCBs) affecting bovine oocyte in vitro maturation (IVM) and developmental competence. In the present study, the role of cumulus cell apoptosis in mediating the toxic effects of PCBs during in vitro maturation has been investigated. Results indicate that exposure of cumulus-oocyte complexes (COCs) to A-1254 significantly induced apoptosis of cumulus cells. Furthermore, A-1254 significantly increased the expression of the pro-apoptotic gene, Bax, concomitantly reducing the level of the anti-apoptotic gene, Bcl-2, in the cumulus cell compartment. The effects of pure mixtures of coplanar (PCB 77, 126 and 169) or non-coplanar (PCB 52, 101 and 153) PCBs were examined. Exposure of COCs to coplanar PCBs affected maturation at doses as low as 100.6 pg/ml. Furthermore, a significant increase in apoptosis and in Bax mRNA expression was observed. No variations in maturation or apoptosis were observed in the non-coplanar PCB group. To further analyze the role of cumulus cells, COCs and denuded oocytes (DOs) have been exposed to A-1254 or coplanar PCBs during IVM. Exposure of COCs significantly reduced the percentage of matured oocytes after 24 h of culture in both treatments. In contrast, exposure of DOs significantly decreased the maturation rate only at the highest dose investigated (100-fold greater than that affecting COCs). Taken together, the results indicate a direct role of cumulus cell apoptosis in mediating PCB toxicity on bovine oocytes, and a direct relationship between congener planarity and toxicity in bovine oocytes is suggested.

Persistent Organochlorine Chemicals in Plasma and Risk of Non-Hodgkin's Lymphoma

Polychlorinated biphenyls (PCB) have been suspected as possible contributors to increasing non-Hodgkin's lymphoma incidence during the latter half of the 20th century based on their toxicologic properties and provocative epidemiologic reports. We investigated PCBs and other organochlorines and risk of non-Hodgkin's lymphoma in a population-based case-control study in the United States. Congeners of PCBs (including coplanar congeners), dioxins, furans and pesticides or pesticide metabolites were measured in plasma of 100 untreated cases and 100 control subjects. We used a multiple imputation procedure to fill in missing values of levels determined to be below the detection limits. Risks of non-Hodgkin's lymphoma associated with each analyte were estimated using conditional logistic regression for the continuous measure, exposure quartiles, trend across quartile categories, and exposures above the 95th percentile. Certain PCB congeners were associated with increased risk of non-Hodgkin's lymphoma, including coplanar PCBs 156, 180, and 194, with odds ratios for the highest versus lowest quartile ranging from 2.7 to 3.5, and significant trends. Each of the furan congeners was associated with risk of non-Hodgkin's lymphoma, as were total furans, with 3.5-fold increased risk for the highest versus lowest quartile and a significant trend across quartiles (P = 0.006). The toxic equivalency quotient (TEQ), a summed metric that weights congeners by their dioxin-like potency, was associated with non-Hodgkin's lymphoma, with 35% increased risk per 10 TEQ pg/g lipid (95% confidence interval, 1.02-1.79). Our results add to existing literature, which suggests that exposure to organochlorines contributes to non-Hodgkin's lymphoma risk; these risks were most apparent for certain PCBs and furans.

Comparison of hepatic and extra hepatic induction of cytochrome P4501A by graded doses of aryl hydrocarbon receptor agonists in Atlantic tomcod from two populations

Atlantic tomcod Microgadus tomcod from the Hudson River, New York, are exposed to high levels of polycyclic aromatic hydrocarbons (PAHs) and bioaccumulate mixtures of polychlorinated biphenyls (PCBs), polychlorinated dibenzo- p-dioxins and polychlorinatedfurans (PCDD/Fs). Previous studies demonstrated that hepatic cytochrome P4501A (CYP1A) mRNA was not inducible in tomcod from the Hudson River treated with single doses of PCB77 or 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), but was inducible with PAHs. In this study, we sought to determine if CYP1A mRNA was inducible with higher doses of these and other halogenated aromatic hydrocarbons (HAHs) in Hudson River tomcod and if decreased sensitivity to gene inducibility occurs across all tissues. Tomcod from the Hudson River and the cleaner Miramichi River, New Brunswick, were treated individually with graded doses of TCDD and coplanar PCBs (PCB77, PCB81, PCB126, PCB169) and profiles of hepatic CYP1A mRNA expression were compared between the two populations. CYP1A mRNA inducibility was also compared in multiple tissues of tomcod from the two rivers that were treated with PCB77. Additionally, hepatic CYP1A mRNA was characterized in Miramichi River tomcod treated with pairs of PCB congeners that included aryl hydrocarbon receptor (AHR) agonists and antagonists. Hepatic CYP1A mRNA was significantly inducible by all agonists in tomcod from the Miramichi River and TCDD and two of four PCBs in tomcod from the Hudson River. CYP1A mRNA was also significantly inducible in four of five tissues of tomcod from the Miramichi River but only in liver of Hudson River tomcod. In summary, CYP1A mRNA inducibility was approximately two orders of magnitude less sensitive in tomcod from the Hudson River than in those from the Miramichi River. But when achieved, maximum levels of CYP1A expression were similar in tomcod from the two populations. Co-administration of PCB126 and PCB77 did not produce significantly greater CYP1A mRNA induction than administration of PCB126 alone and co-administration of mono- ortho-substituted PCB105 significantly decreased CYP1A mRNA inducibility by PCB77. These results indicate that CYP1A mRNA expression is significantly inducible by HAHs in tomcod from the Hudson River and suggest that all components of the AHR pathway are present and functional, but that the pathway is less sensitive to activation than in tomcod from the Miramichi River. Our results also indicate that CYP1A mRNA levels in environmentally exposed fish may not reflect additive tissue burdens of PCB congeners.

Differential effects of PCBs on the induction of apoptosis machinery and PKCα translocation in rat renal tubular cell cultures

We have demonstrated previously [Pérez-Reyes, P.L., Sánchez-Alonso, J.A., López-Aparicio, P., Recio, M.N., Pérez-Albarsanz, M.A., 2001. Different molecular capacity in the induction of apoptosis by polychlorinated biphenyl congeners in rat renal tubular cell cultures. Biosci. Rep. 6, 765–778] that the polychlorinated biphenyls (PCBs) cause loss of cell viability and accelerate apoptosis in cell kidney cultures. Further investigations are necessary to elucidate the mechanism of apoptosis induction. In this way, we have analyzed in the present work the effects of PCBs on protein kinase C (PKC, a protein family intimately involved in the regulation of cell survival) and the expression of two proapoptotic (caspase-3 and Bax) and one antiapoptotic (Bcl-2) proteins. Aroclor 1248 (a commercial PCB mixture with 48% chlorine by weight), PCB 153 (2,2′,4,4′,5,5′-hexachlorobiphenyl, a di- ortho-substituted nonplanar congener) and PCB 77 (3,3′,4,4′-tetrachlorobiphenyl, a non- ortho-substituted planar congener), significantly increased PKCα activity compared to control cells in the cytosolic and particulate cell fractions, and increased the PKCα protein content in the particulate fraction. The nonplanar PCB 153 showed stronger effects than the coplanar congener PCB 77. In addition, Aroclor 1248 decreased both, procaspase-3 levels and the Bcl-2/Bax protein ratio. These findings indicate that PCBs, particularly nonplanar congeners, can induce apoptosis in primary renal tubular cells through the PKCα, caspase-3 and Bcl-2/Bax pathway.

Non-Coplanar PCB-Mediated Modulation of Human Leukocyte Phagocytosis: A New Mechanism for Immunotoxicity

Organochlorine (OC) contaminants, notably polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are ubiquitous in all ecosystems and found in the tissues of humans and wildlife. Although the immunotoxicity of coplanar, dioxinlike PCBs is well documented, the adverse effects exerted by non-coplanar, non-dioxinlike PCBs have received little attention. Direct causal relationship between PCB and dioxin exposure and the observed detrimental effects on the immune system has yet to be fully established in humans. The immunomodulatory potential of toxic coplanar PCB 169 and TCDD and abundant non-coplanar PCBs 138, 153, and 180 on human leukocyte phagocytosis, an important innate immune function that initiates the clearance of pathogens, was tested upon in vitro exposure. Mixture and concentration-response experiments demonstrated a suppression of phagocytosis by non-coplanar PCBs suggesting a previously unrecognized aryl hydrocarbon receptor (AhR)-independent pathway. Regression analysis revealed that reduction of phagocytosis was mostly explained by the non-coplanar congeners. The effects on phagocytosis could not be accurately predicted by either the currently used toxic equivalence (TEQ) approach or the mouse model, thus undermining the use of the traditional models in the risk assessment for OC mixtures containing non-coplanar congeners. Our results are cause for concern as they suggest an AhR-independent pathway through which non-coplanar PCBs modulate phagocytosis, the immune system's first line of defense, possibly increasing the risk to developing infectious disease.

Reference values of coplanar and non-coplanar PCBs in serum samples from two Italian population groups

The main goal of this study is to establish the reference values of individual Polychlorinated biphenyl (PCB) congeners in non-occupationally exposed subjects. Since the PCB pattern in human serum is related to the living area, two different population groups from North and Central Italy, were compared. Serum concentrations of both coplanar and non-coplanar PCB congeners were measured by using gas chromatography coupled with low-resolution mass spectrometry (HRGC–LRMS). A fast and reliable method for the determination of 60 congeners had been previously validated. Its reliability was further verified by using high-resolution mass spectrometry. Thirty-one congeners out of 60 were found at detectable concentrations in at least one sample. The mean value for total PCBs was found to be 2.48 and 3.93 μg/L for the two population groups. Eight dioxin-like PCBs were detected. In accordance with the findings from the literature, the most abundant congeners were found to be 153, 138, 180, and 170. Both univariate and multivariate analysis showed that age is a significant determinant of PCB concentrations. The correlation increased with increasing chlorination. Slight differences in the PCB pattern were observed in the two population groups.

Production Mechanism of Hydroxylated PCBs by Oxidative Degradation of Selected PCBs Using TiO2 in Water and Estrogenic Activity of Their Intermediates

The oxidative photodegradation behaviors of selected polychlorinated biphenyls (PCBs) [2,3,3',4'-tetraCB (BZ number: CB56), 2,3',4',5-tetraCB (CB70), and 3,4,4',5-tetraCB (CB81: coplanar PCB)] using titanium dioxide (TiO2) in water were investigated. The main purposes were to clarify the structural relation between the original PCBs and the intermediates derived by TiO2 oxidation and to evaluate the estrogenic activity in the treated PCBs during the oxidative reactions. Approximately 90% of the three tetraCBs decomposed within 120 min. Intermediates by decomposition of three tetraCBs, such as some OH-tetraCBs and OH-triCBs, carboxylic intermediates, phenolic intermediates, and other intermediates produced by the cleavage of a benzene ring were identified and quantified. In the degradation pathways, the produced amounts of OH-tetraCB and OH-triCB increased within 60 min of irradiation time. Estrogenic activities of the intermediates from the three tetraCBs in water were assessed by using a yeast two-hybrid assay system for human estrogen receptor alpha (hERalpha). The maximal estrogenic activities were induced by the solutions of decomposed CB81 with irradiation time at 60 min. We found that the solutions at an irradiation time of 60-120 min contained several 4-OH-tetraCBs and 4-OH-triCBs substituted with OH and Cl at para- and para'-positions. It is presumed that the chemical structures of the 4-OH-PCBs are similar to that of 17beta-estradiol (beta-E2); these intermediates present strong estrogenic activities. Moreover, we learned that there is a high possibility of conversion from some low toxic PCBs congeners to strong estrogenic OH-PCBs.

Consumption advisories for salmon based on risk of cancer and noncancer health effects

The levels of dioxins/furans, polychlorinated biphenyls (PCBs), and chlorinated pesticides were determined in farmed salmon for eight regions in Europe, North America, and South America, in salmon fillets purchased in 16 cities in Europe and North America, and in five species of wild Pacific salmon. Upon application of US Environmental Protection Agency (USEPA) methods for developing fish consumption advisories for cancer from mixtures of all of these substance for which USEPA has reported a cancer slope factor, the most stringent recommendation, for farmed salmon from northern Europe, was for consumption of at most one meal every 5 months in order to not exceed an elevated risk of cancer of more than 1 in 100,000. Farmed salmon from North and South America triggered advisories of between 0.4 and one meal per month. Retail market samples, in general, reflected levels found in regionally farmed fish, although much of the US salmon comes from Chile, which had somewhat lower contaminant levels than the North American farmed samples. Upon consideration of all of these organochlorine compounds as a mixture, even wild Pacific salmon triggered advisories of between one and less than five meals per month. The advisories are driven by the nondioxin-like PCBs and pesticides and not by dioxins/furans and coplanar PCBs. For noncancer effects for contaminants where USEPA has provided a reference dose only endrin and PCBs triggered any significant advisory. For both of these in the worst case, farmed salmon from northern Europe, the advice was not more than three meals per month.

Induction of Cytochrome P450 1A5 mRNA, Protein and Enzymatic Activities by Dioxin-Like Compounds, and Congener-Specific Metabolism and Sequestration in the Liver of Wild Jungle Crow (Corvus macrorhynchos) from Tokyo, Japan

This study presents concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxin-like coplanar PCBs (Co-PCBs) in the liver and breast muscle of jungle crows (JCs; Corvus macrorhynchos) collected from Tokyo, Japan. 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) derived by WHO bird-TEF were in the range of 23 to 280 pg/g (lipid) in the liver, which are lower or comparable to the lowest-observed-effect-level of CYP induction in chicken, and 5.6-78 pg/g (lipid) in the pectoral muscle. Cytochrome P450 (CYP) 1A-, 2B-, 2C-, and 3A-like proteins were detected using anti-rat CYP polyclonal antibodies in hepatic microsomal fractions. Significant (p < 0.05) positive correlations between hepatic TEQs and CYP1A or CYP3A-like protein expression levels were noticed, implying induction of these CYP isozymes by TEQs. On the other hand, there was no significant positive correlation between muscle TEQ and any one of analyzed CYP isozyme expression levels. CYP1A- and CYP3A-like protein expression levels represented better correlations with pentoxy- and benzyloxyresorufin-O-dealkylase activities rather than methoxy- and ethoxyresorufin-O-dealkylase activities, indicating unique catalytic functions of these CYPs in JCs. Furthermore, we succeeded in isolating CYP1A5 cDNA from the liver of JC, having an open reading frame of 531 amino acid residues with a predicted molecular mass of 60.3 kDa. JC CYP1A5 mRNA expression measured by real-time RT-PCR had a significant positive correlation with hepatic TEQs, suggesting induction of CYP1A5 at the transcriptional level. Ratios of several Co-PCB congeners to CB-169 in the liver of JCs revealed significant negative correlations with CYP1A protein or CYP1A5 mRNA expression levels, implying metabolism of these congeners by the induced CYP1A. The liver/breast muscle concentration (L/M) ratios of PCDDs/DFs and CB-169 increased with an increase in hepatic CYP1A protein or CYP1A5 mRNA expression levels, suggesting congener-specific hepatic sequestrations by the induced CYP1A. The present study provides insights into the propensity of CYP1A induction to the exposure of dioxin-like chemicals, and unique metabolic and sequestration capacities of CYP1A in JC.

Biological responses to PCB exposure in shorthorn sculpin from Saglek Bay, Labrador

A local source of polychlorinated biphenyls (PCBs) in Saglek Bay, Labrador, has contaminated marine sediments and the coastal food web. As part of a larger assessment of ecological risks in the Bay, we evaluated biological responses to PCB concentrations in a northern fish species, the shorthorn sculpin ( Myoxocephalus scorpius). Biological endpoints, including ethoxyresorufin- O-deethylase (EROD) activity in liver tissue, fish body condition, lipid content, and relative liver mass were examined in 35 sculpin collected during August–September 1999. Across a wide range of PCB concentrations (5.1–6920 ng/g wet weight (ww) in whole fish excluding liver), sculpin showed significant EROD induction (as much as 25-fold in the most exposed group). Responses varied directly with PCB concentrations but there was also an apparent threshold for induction at about 50 ng/g ww (whole fish excluding liver). A strong relationship between sculpin PCB concentrations and the concentrations of PCBs in the marine sediments of Saglek Bay suggests that concentrations above this threshold can arise from very low concentrations in sediments (2.3 ng/g dry weight). Other biological endpoints did not show significant responses to PCB concentrations, nor were they related to the observed EROD activity. Although PCDF compounds were present in trace amounts (primarily 2,3,4,7,8-PnCDF), mono- ortho and non- ortho substituted (coplanar) PCBs appeared to contribute the majority of the total dioxin toxic equivalent (TEQ) concentrations. Overall, the results indicate that biological responses occur in shorthorn sculpin with relatively low PCB concentrations (∼50 ng/g), which are not unrealistic for even mildly contaminated areas in northern Canada.

Levels and Trends of Polychlorinated Dibenzo-p-dioxins/Furans (PCDD/Fs) and Dioxin-like Polychlorinated Biphenyls (PCBs) in Spanish Commercial Fish and Shellfish Products, 1995−2003

The polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and polychlorinated biphenyl (PCB) contents of 123 Spanish commercial salmon, tuna fish, sardine, oyster, mussel, and clam samples from 1995 to 2003 were investigated. A significant decrease of dioxin and non-ortho PCB concentrations in the studied species was found over the years. The decrease was greater in the case of dioxins than in that of non-ortho PCBs, especially during the early years of the study. PCB and PCDD/F concentrations in the years 2001-2003 were comparable to those reported in the literature for similar species collected after 1999. Mean PCB concentrations ranged from 3.46 ng/g of fresh weight (fw) in clams to 100 ng/g of fw in tuna fish. PCDD/F mean current levels ranged from 0.62 pg/g of fw in clams to 2.89 pg/g of fw in oysters. Toxic equivalent quantities (WHO-TEQ) ranged from 0.05 pg of WHO-TEQ(PCDD/Fs)/g of fw in clams to 0.5 pg of WHO-TEQ(PCDD/Fs)/g of fw in salmon (in the upper bound determination levels). When coplanar PCBs were included, the WHO-TEQ(PCDD/Fs+cop) (PCBs) values increased by a range of 1.7 times in oysters to 14.1 times in tuna fish. The decrease in dioxin concentrations suggests that efforts to control dioxin emissions and to reduce human exposure through foodstuffs are succeeding. The high contribution of PCBs to total WHO-TEQs in the fish and shellfish species investigated suggests that it is important to determine PCBs in foodstuffs, and especially in fish products, and they should be included in further research and future legislation.

PCDDs, PCDFs, and coplanar PCBs in wild terrestrial mammals from Japan: Congener specific accumulation and hepatic sequestration

The present study determined the contamination levels and congener-specific accumulation features of dioxins and related compounds (DRCs) in wild terrestrial mammals such as large Japanese field mice (LJFM), lesser Japanese moles (LJMs), and raccoon dogs (RDs) collected from Kanto region in Japan during 2001. The toxic equivalent quantity (TEQ) levels in the carcasses or adipose tissues were in the order of RDs ≥ LJMs > LJFM. Comparison of DRC congener profiles in the three species and principal component analysis (PCA) demonstrated a higher contribution of OCDD, T 4CB77, and P 5CB118 in LJMs. Analysis of liver-adipose distribution of DRC congeners in RDs showed that livers contained significantly higher TEQs than adipose tissues, indicating that liver is a depository organ and critical for determining the toxicokinetics of DRCs. As for most T 4, P 5, H 6CDD/DFs and for P 5CB126, H 6CB169 and mono- ortho PCB congeners, their liver/adipose concentration ratios in RDs revealed a tendency to increase with hepatic TEQ levels, suggesting TEQ-dependent hepatic sequestration.

Human milk survey for dioxins in the general population in Japan

Background Much attention has been paid to the level of dioxins in breast milk in Japan but few large-scale studies have been conducted on the subject. Methods From 1997 to 2002, we collected 839 samples of breast milk from primiparas residing throughout Japan. Starting in 1999, breast milk was also collected from secundiparas. Seven isomers of polychlorinated dibenzo- p-dioxins (PCDDs), 10 of polychlorinated dibenzofurans (PCDFs), 4 of coplanar polychlorinated biphenyls (Co-PCBs) and 8 of mono-orthochlorinated polychlorinated biphenyls (mono-ortho PCBs) were analyzed by employing gas chromatography and mass spectrometry. A correlation between the level of dioxins in human milk and the age of the mothers was noted for the primiparas and the secundiparas; and the levels were compared between the first and the second deliveries. Grouped by parity and prefecture in each year, observations were also made on the trends in these levels. Dioxin levels are shown by using geometric means because their distributions were skewed to the left. Results The sum of PCDDs and PCDFs, Co-PCBs, mono-ortho PCBs, and total dioxins in the breast milk of primiparas were 13.9, 5.4, 3.4, and 22.7 pg TEQ/g fat, respectively. In the samples obtained from secundiparas, these levels were 63–68 percents of those taken from the primiparas. The correlation coefficients between the PCDDs/DFs, Co-PCBs, mono-ortho PCBs, and total dioxins and the age of the primiparas were 0.19, 0.17, 0.36, and 0.24, respectively. All these correlations were statistically significant ( p < 0.001). The positive correlations between these contaminants and the age of the secundiparas were also examined. The total dioxins as well as PCDDs/DFs, Co-PCBs, and mono-ortho PCBs in the breast milk of the primiparas declined significantly between 1998 and 2002 (regression coefficients: −0.04, −0.05, −0.03, and −0.03, respectively). However, no significant decline in these levels was observed when sorted by prefectures. Conclusions Much attention should be paid to the age and parity of nursing mothers when investigating the relationship between the level of dioxins in breast milk and the body burden of infants.

Coplanar Polychlorinated Biphenyls Activate the Aryl Hydrocarbon Receptor in Developing Tissues of Two TCDD-Responsive lacZ Mouse Lines

In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can have an immediate impact on developmental processes that then lead to long-term deficits in function. To define the specific tissues affected by TCDD during development, we developed a lacZ-reporter gene mouse model driven by activation of the aryl hydrocarbon receptor (AhR). Exposure to TCDD on gestational day (GD) 14 results in strong activation of the lacZ transgene in numerous tissues including fore and hind paws, ear, and genital tubercle. Experiments were conducted to examine the ability of alternative AhR ligands to activate our model system. The coplanar polychlorinated biphenyl congeners 3,4,5,3',4'-pentachlorobiphenyl (PCB126) and 3,4,3',4'-tetrachlorobiphenyl (PCB77) both induced staining in fetal tissues identical to that observed following TCDD exposure. Exposure of fetuses to the PCB mixture Aroclor 1254 and the non-coplanar congener 2,3,6,2',5'-pentachlorobiphenyl (PCB95) did not result in any activation of the lacZ transgene. In addition to the testing of alternative ligands, another line of reporter mice was generated to determine the potential influence of the site of insertion of the lacZ transgene on the reported observations. Both TCDD and the coplanar PCBs induced a similar pattern of staining in the new line as compared to that observed in the original lacZ reporter mouse line. The ability of AhR ligands, other than TCDD, to activate the AhR-mediated transgene, in combination with the insertion-site independence of the response, strengthens the data previously derived from this model and increases the utility of this system for investigations examining AhR-mediated events during development.

Extractability of dioxins from soil: II. Effects of acid or alkaline pretreatment on the extractability of dioxin homologues from soil samples

The effects of sample pretreatment on the extractability of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (CoPCBs) from three suburban soil samples were evaluated. The samples were treated with 0.1 M HCl or 0.1 M NaOH and extracted by pressurized liquid extraction (PLE) with toluene. In addition, untreated soil samples were subjected to PLE with acetone. The extractability values were compared to values obtained by toluene extraction without pretreatment. Alkaline pretreatment increased the extractability of higher-chlorinated CDDs (HiCDDs), whereas acid pretreatment slightly decreased their extractability. No change in extractability was observed for higher-chlorinated CDFs under any conditions. The extractability of lower-chlorinated CDD/Fs (LoCDD/Fs) and CoPCBs was increased only by acetone extraction. PCDD/F homologue profiles in soil humic acid fractions and those in dead leaves, a major raw material of soil humus, were also determined. These results suggest that the variations in the extractability of dioxin homologues are due mainly to variations in their physical state in the soil, especially their interactions with soil humus.

Polychlorinated Biphenyls and Organochlorine Pesticides in Human Adipose Tissue and Breast Milk Collected in Hong Kong

Contamination from persistent organic pollutants is a pervasive global problem that urgently demands global concern and action. In the present study, concentrations of organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs) were determined in 37 samples of female adipose tissue collected in Hong Kong hospitals. Among the pollutants analyzed, DDTs (2.79 ng/g fat), HCHs (0.72 ng/g fat), and PCBs (0.19 ng/g fat) were prominent compounds in most of the adipose tissue. p,p'-DDE and hexachlorinated biphenyls were found in all samples, whereas heptachlor epoxide and dieldrin were found only in some samples. An estimation of toxic equivalency concentration (TEQ) due to dioxin-like coplanar PCBs was also performed. The estimated TEQ(PCBs) was 2.01 pg/g fat. This study also compared our previous results obtained from the milk samples of the same donors. Significant correlations are obtained for DDTs and HCHs between milk and adipose tissue. Detailed review of available information concerning OC pesticides and PCBs in different ecological compartments indicated that bioconcentration and biomagnification of these contaminants are common phenomena of the Pearl River Delta region, which has undergone rapid socioeconomic change in the past 20 years. It is suggested to establish a regional organization in order to coordinate the monitoring of persistent organic pollutants in the region.