TCDD Equivalents Research Articles

Re-evaluation of TEFs for dioxin-like PCDDs, PCDFs, and PCBs for fishes.

An expert meeting was organized by the World Health Organization (WHO) in 1997 to streamline assessments of risk posed by mixtures of dioxin-like chemicals (DLCs) through development of TCDD equivalency factors (TEFs) for mammals, birds, and fishes. No re-evaluation has been performed for fish TEFs. Therefore, the objective of the present study was to re-evaluate the TEFs for fishes based on an updated database of relative potencies (RePs) for DLCs. Selection criteria consistent with the WHO meeting resulted in 53 RePs across fourteen species of fish ultimately being considered. Of these RePs, 70% were not available at the time of the WHO meeting. These RePs were used to develop updated TEFs for fishes based on a similar decision process as the WHO meeting. The updated TEF for sixteen DLCs was greater than the WHO TEF, but only four differed by more than an order of magnitude. Measured concentrations of DLCs in four environmental samples were used to compare TCDD equivalents (TEQs) calculated using the WHO TEFs relative to the updated TEFs. The TEQs for none of these environmental samples differed by more than an order of magnitude. Therefore, present knowledge supports that the WHO TEFs are suitable potency estimates for fishes. However, the updated TEFs pull from a larger database with a greater breadth of data and as a result offer greater confidence relative to the WHO TEFs. Risk assessors will have different criteria in selection of TEFs, and the updated TEFs are not meant to immediately replace the formal WHO TEFs; but those who value a larger database and increased confidence in TEQs could consider using the updated TEFs.

Pentachlorophenol, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans in surface soil surrounding pentachlorophenol-treated utility poles on the Kenai National Wildlife Refuge, Alaska USA

Composite surface soil samples were collected at 0, 25, and 50 cm from the base of 12 utility poles on the Kenai National Wildlife Refuge in Alaska, to assess the extent to which pentachlorophenol, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans may have leached from pentachlorophenol-treated poles. Six pairs of utility poles were included, consisting of an “old” pole manufactured in 1959 or 1963, a “new” pole manufactured within the past 20 years, and a suitable background soil sample from the same vicinity. Old poles had greater concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs) near the pole base and at 25 cm than “new” poles did. For all 12 poles combined, the mean pentachlorophenol levels in soil were 1810, 157, and 17.8 ppm dry weight (d.w.) near the pole bases, at 25 and 50 cm from the poles, respectively, while the mean total TEQ levels in soil were 15,200, 5170, and 1510 parts per trillion d.w. at those distances. Surface soil levels of pentachlorophenol and TCDD-TEQs exceeded both human health and ecological risk-based screening levels. The design and results of this study were similar to another project in Montreal, Quebec in Canada. Together the results are cause for concern, indicating that millions of similarly treated utility poles in North America may be point sources of pentachlorophenol and dioxins/furans to soil.

Toxicological and chemical insights into representative source and drinking water in eastern China.

Drinking water safety is continuously threatened by the emergence of numerous toxic organic pollutants (TOPs) in environmental waters. In this study, an approach integrating invitro bioassays and chemical analyses was performed to explore toxicological profiles of representative source and drinking water from waterworks of the Yangtze River (Yz), Taihu Lake (Th), and the Huaihe River (Hh) basins in eastern China. Overall, 34 of 96 TOPs were detected in all water samples, with higher concentrations in both source and drinking water samples of Hh, and pollutant profiles also differed across different river basins. Non-specific bioassays indicated that source water samples of Hh waterworks showed higher genotoxicity and mutagenicity than samples of Yz and Th. An EROD assay demonstrated dioxin-like toxicity which was detected in 5 of 7 source water samples, with toxin concentration levels ranging from 62.40 to 115.51 picograms TCDD equivalents per liter of water (eq./L). PAHs and PCBs were not the main contributors to observed dioxin-like toxicity in detected samples. All source water samples induced estrogenic activities of 8.00-129.00 nanograms 17β-estradiol eq./L, and estrogens, including 17α-ethinylestradiol and estriol, contributed 40.38-84.15% of the observed activities in examined samples. While drinking water treatments efficiently removed TOPs and their toxic effects, and estrogenic activity was still observed in drinking water samples of Hh. Altogether, this study indicated that the representative source water in eastern China, especially that found in Hh, may negatively affect human health, a finding that demonstrates an urgent requirement for advanced drinking water treatments.

Detoxifying Effects Of A Diet-Based Multidisciplinary Intervention Program

Background: Current studies have shown that environmental pollutants including aryl hydrocarbon receptor(AhR) ligands contribute negatively to a wide range of human diseases and pathological conditions. No useful intervention method, however, has been recommended to reduce the pollutants accumulated in the human body yet. In this study, we developed a dietary-based multidisciplinary program and evaluated its detoxifying effects using the AhR ligand binding activity in serum. Methods: Twenty-eight subjects participated in the program for 3 weeks(20 women and 8 men; mean age of 45.9±15.1 years). The participants followed the multidisciplinary program with a well-balanced diet, which consisted of gluten-free, germinated brown rice-centered vegetable liquid meals for breakfast and dinner, and regular meals for lunch. Additionally, participants were taught to perform regular exercise for over 15 min and breathing meditation for 15 minutes. Serum AhR ligand binding activities, which were expressed as TCDD equivalents. To see the effect of the intervention on reducing the pollutants, AhR ligand binding was checked before and after the intervention program in all subjects. In addition, changes in anthropometric and metabolic parameters were checked. Results: AhR ligand binding activities were significantly decreased after 3 weeks(-0.3±0.2pmol/L, P

Functionality of aryl hydrocarbon receptors (AhR1 and AhR2) of white sturgeon (Acipenser transmontanus) and implications for the risk assessment of dioxin-like compounds.

Worldwide, populations of sturgeons are endangered, and it is hypothesized that anthropogenic chemicals, including dioxin-like compounds (DLCs), might be contributing to the observed declines in populations. DLCs elicit their toxic action through activation of the aryl hydrocarbon receptor (AhR), which is believed to regulate most, if not all, adverse effects associated with exposure to these chemicals. Currently, risk assessment of DLCs in fishes uses toxic equivalency factors (TEFs) developed for the World Health Organization (WHO) that are based on studies of embryo-lethality with salmonids. However, there is a lack of knowledge of the sensitivity of sturgeons to DLCs, and it is uncertain whether TEFs developed by the WHO are protective of these fishes. Sturgeons are evolutionarily distinct from salmonids, and the AhRs of sturgeons differ from those of salmonids. Therefore, this study investigated the sensitivity of white sturgeon (Acipenser transmontanus) to DLCs in vitro via the use of luciferase reporter gene assays using COS-7 cells transfected with AhR1 or AhR2 of white sturgeon. Specifically, activation and relative potencies (RePs) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachloro-dibenzofuran, 2,3,7,8-tetrachloro-dibenzofuran, 3,3',4,4',5-pentachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, and 2,3,3',4,4'-pentachlorobiphenyl were determined for each AhR. It was demonstrated that white sturgeon expresses AhR1s and AhR2s that are both activated by DLCs with EC50 values for 2,3,7,8-TCDD that are lower than those of any other AhR of vertebrates tested to date. Both AhRs of white sturgeon had RePs for polychlorinated dibenzofurans more similar to TEFs for birds, while RePs for polychlorinated biphenyls were most similar to TEFs for fishes. Measured concentrations of select DLCs in tissues of white sturgeon from British Columbia, Canada, were used to calculate toxic equivalents (TEQs) by use of TEFs for fishes used by the WHO and TCDD equivalents (TCDD-EQs) via the use of RePs for AhR2 of white sturgeon as determined by transfected COS-7 cells. TCDD-EQs calculated for endangered populations of white sturgeon were approximately 10-fold greater than TEQs and were within ranges known to cause adverse effects in other fishes, including other species of sturgeons. Therefore, TEFs used by the WHO might not adequately protect white sturgeon, illuminating the need for additional investigation into the sensitivity of these fish to DLCs.

Instrumental and bioanalytical measures of dioxin-like compounds and activities in sediments of the Pohang Area, Korea

Pohang is a mid-sized city in which Korea's largest manufacturer of steel is located. The Hyeongsan River, which runs through Pohang and empties into Yeongil Bay, is therefore expected to be affected by various municipal and industrial inputs. In order to characterize aryl hydrocarbon receptor (AhR)-mediated activities in sediments from the Pohang area, a total of eight locations along the Hyeongsan River were chosen and 16 sediment samples were collected during two sampling campaigns in 2010. Organic extracts of sediments were characterized by both quantitative chemical analyses of dioxin-like chemicals and the in vitro H4IIE-luc bioassay. Significant dioxin-like activities were observed in sediments from industrial and municipal areas, which indicates that most of the dioxin-like chemicals were associated with surrounding anthropogenic sources. In general, responses of the H4IIE-luc assay were significantly correlated with concentrations of target compounds including dioxins, furans, co-planar PCBs, and dioxin-like PAHs. A potency balance analysis indicated that instrumentally derived TCDD equivalents (TEQs) explained about 77% of the bioassay-derived TCDD equivalents (TCDD-EQs). Among the target chemicals measured, certain penta-chlorinated dioxin and furan compounds accounted for the majority of dioxin-like activities associated with sediments. Compositional analysis of target chemicals the sources of such dioxin-like activities were mainly derived from the local activities such as the iron and steel industries. Concentrations and activities of AhR agonists were similar to what was measured approximately 10years ago. Thus, while AhR agonists seem to be persistent in sediments there seem to have been no large increases in these chemicals in the Pohang area.

Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy.

Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity-related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell-based arylhydrocarbon receptor (AhR)-dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes. We enrolled diabetic patients with normoalbuminuria (n=36), microalbuminuria (n=29), macroalbuminuria (n=8) and end-stage renal disease (n=31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and expressed as TCDD equivalents (TCDDeqpmol/L). Mean serum AHRT activities were higher in patients with microalbuminuria (40.1±7.1pmol/L), macroalbuminuria (37.4±5.5pmol/L) and end-stage renal disease (59.1±20.0pmol/L) than in subjects with normoalbuminuria (12.7±5.4pmol/L; P<0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR; r=-0.663, P<0.001), serum creatinine level (r=0.635, P<0.001), systolic blood pressure (r=0.223, P=0.026), glycated hemoglobim (r=0.339, P<0.001) and diabetic duration (r=0.394, P<0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors. The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy.

Environmental contamination and human exposure to dioxin-related compounds in e-waste recycling sites of developing countries

E-waste recycling using uncontrolled processes is a major source of dioxin-related compounds (DRCs), including not only the regulated polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) but also non-regulated brominated and mixed halogenated compounds (PBDD/Fs and PXDD/Fs). Various studies at informal e-waste recycling sites (EWRSs) in Asian developing countries found the soil contamination levels of PCDD/Fs from tens to ten thousand picogram TCDD-equivalents (TEQ) per gram and those of DL-PCBs up to hundreds of picogram TEQ per gram. The air concentration of PCDD/Fs was reported as high as 50 pg TEQ per m(3) in Guiyu, the largest Chinese EWRS. Non-regulated compounds also contributed substantially to the total DL toxicity of the DRC mixtures from e-waste, as evidenced by the high TEQ levels estimated for the currently identifiable PBDD/Fs as well as the large portion of unexplained bioassay-derived TEQ levels in soils/dusts from EWRSs. Considering the high exposure levels estimated for EWRS residents, especially children, comprehensive emission inventories of DRCs from informal e-waste recycling, the identities and toxic potencies of unidentified DRCs released, and their impacts on human health need to be investigated in future studies.

Degradative fate of 3-chlorocarbazole and 3,6-dichlorocarbazole in soil

3-Chlorocarbazole and 3,6-dichlorocarbazole were isolated from Bavarian soils. The stereospecific formation of the isomers of these chlorinated carbazols can be explained by quantum mechanical calculations using the DFT method. It was shown that chlorination of carbazole and 3-chlorocarbazole respectively is preferred via the sigma-complexes 3-chlorocarbazole and 3,6-dichlorocarbazole as the most stable products. The dioxin-like toxicological potential of 3,6-dichlorocarbazole, determined by the Micro-EROD Test, is in the range of some picogram TCDD equivalents per milligram carbazole. The degradative fate of 3-chlorocarbazole and 3,6-dichlorocarbazole was analysed within a long-term study (57days) in soil. The soil was extracted by ASE (accelerated solvent extraction) and a further clean-up procedure with column chromatography and chromatography with C18-SPE stationary phases. Quantification of 3-chlorocarbazole and 3,6-dichlorocarbazole was performed employing the isotope-dilution method. The samples were measured with high-resolution GC/MS. The degradation (ln(c/c(0)) vs. time with best-fit line) showed in almost every storage condition a very small degradation (slopes (h(-1)) in -10(-4) range). However, the decay for the controls were two to three times (-28°C) and six times (with sodium azide) higher, than the decrease of 3-chlorocarbazole and 3,6-dichlorocarbazole in the samples of environmental conditions. Especially because of the toxicological potential of 3-chlorocarbazole and 3,6-dichlorocarbazole the proven degradative fate is of large interest. The results show that the analysed carbazoles are not readily degradable in this time period. The expected results of exponential decay behaviour could not be proven. Longer-lasting studies are expected to reveal more accurate half-lives, although it has been shown here, that the compounds are not readily degradable in their native soil environment.

High-throughput screening of dioxins in sediment and soil using selective pressurized liquid extraction with immunochemical detection

A high-throughput screening method using selective pressurized liquid extraction (SPLE) and enzyme-linked immunosorbent assay (ELISA) for monitoring dioxins in sediment and soil is described. SPLE conditions were developed by extracting sediment or soil together with alumina, 10% AgNO 3 in silica, and sulfuric acid impregnated silica (acid silica) using dichloromethane (DCM) as the solvent at 100 °C and 2000 psi. Post-extraction cleanups were not required for ELISA. Two reference sediments (National Institute of Standards and Technology SRM 1944 and Wellington Laboratories WMS01) were analyzed by the SPLE–ELISA method. The ELISA utilized a polyclonal antibody and 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) as the calibrant. Recoveries of ELISA-derived TCDD equivalents (EQ) relative to the expected gas chromatography/high resolution mass spectrometry (GC/HRMS) derived dioxin toxic equivalent (TEQ) values were 116 ± 11% for SRM 1944 and 102 ± 13% for WMS01. ELISA TCDD EQs were consistent with the dioxin TEQs as measured by GC/HRMS for 25 soil/sediment samples from seven different contaminated sites. The ELISA had an approximate method detection limit of 10 pg g −1 with a precision of 2.6–29% based on the relative percentage difference (%RPD) for duplicate samples. Estimated sample throughput for the SPLE–ELISA was three times or more than that of the GC/HRMS method employing PLE with a multi-column cleanup.

Dioxin-like compounds in agricultural soils near e-waste recycling sites from Taizhou area, China: Chemical and bioanalytical characterization

The crude recycling of electronic and electric waste (e-waste) is now creating a new set of environmental problems especially in developing countries such as China. The present study aimed to characterize the dioxin-like compounds in Taizhou area, one of the largest e-waste recycling centers in China, using both chemical analysis and in vitro bioassay. Agricultural soil samples were screened for aryl hydrocarbon receptor (AhR) activity with EROD bioassay in H4IIE cells, and the concentrations of the target AhR agonists including polychlorinated dibenzo- p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) were determined by instruments. The bioassay-derived TCDD equivalents (TEQ bio) and the chemical-calculated TCDD equivalents (TEQ cal) were then compared, and mass balance analysis was conducted to identify the contributors of the observed response. Raw soil extracts from all locations induced significant AhR activities, where the TEQ bio ranged from 5.3 to 210 pg/g dry weight soil (pg/g dw). The total concentrations of 17 PCDD/Fs, 36 PCBs and 16 PAHs varied from 210 to 850 pg/g dw, 11 to 100 ng/g dw, and 330 to 20,000 ng/g dw, respectively. Profile characterization of the target analytes revealed that there were similar sources originating from the crude dismantling of electric power equipments and the open burning of e-waste. There was a significant relationship between TEQ cal and TEQ bio ( r = 0.99, p < 0.05). Based on the mass balance analysis, PCDD/Fs, PCBs and PAHs could account for the observed AhR responses in vitro elicited by soil extracts, though their respective contributions varied depending on sample location. In this study, the combination of chemical analysis and bioanalytical measurements proved valuable for screening, identifying and prioritizing the causative agents within complex environmental matrices.

Neonatal Thyroid Function in Seveso 25 Years after Maternal Exposure to Dioxin

BackgroundNeonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy.Methods and FindingsBetween 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i) a residence-based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination), and 1,772 age-matched women from the surrounding noncontaminated area (reference); (ii) a biomarker study on 51 mother–child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid-stimulating hormone (b-TSH) was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b-TSH was 0.98 μU/ml (95% confidence interval [CI] 0.90–1.08) in the reference area (n = 533), 1.35 μU/ml (95% CI 1.22–1.49) in zone B (n = 425), and 1.66 μU/ml (95% CI 1.19–2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b-TSH > 5 μU/ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001). Neonatal b-TSH was correlated with current maternal plasma TCDD (n = 51, β = 0.47, p < 0.001) and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, β = 0.45, p = 0.005).ConclusionsOur data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure.

Relative potency based on hepatic enzyme induction predicts immunosuppressive effects of a mixture of PCDDS/PCDFS and PCBS

The toxic equivalency factor (TEF) approach was employed to compare immunotoxic potency of mixtures containing polychlorinated dibenzo- p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls relative to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), using the antibody response to sheep erythrocytes (SRBC). Mixture-1 (MIX-1) contained TCDD, 1,2,3,7,8-pentachlorodibenzo- p-dioxin (PeCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), and 1,2,3,4,6,7,8,9-octachlorodibenzofuran (OCDF). Mixture-2 (MIX-2) contained MIX-1 and the following PCBs, 3,3′,4,4′-tetrachlorobiphenyl (IUPAC No. 77), 3,3′,4,4′,5-pentachlorobiphenyl (126), 3,3′,4,4′,5,5 N-hexachlorobiphenyl (169), 2,3,3′,4,4′-pentachlorobiphenyl (105), 2,3′,4,4′,5-pentachlorobiphenyl (118), and 2,3,3′,4,4′,5-hexachlorobiphenyl (156). The mixture compositions were based on relative chemical concentrations in food and human tissues. TCDD equivalents (TEQ) of the mixture were estimated using relative potency factors from hepatic enzyme induction in mice [DeVito, M.J., Diliberto, J.J., Ross, D.G., Menache, M.G., Birnbaum, L.S., 1997. Dose–response relationships for polyhalogenated dioxins and dibenzofurans following subchronic treatment in mice. I .CYP1A1 and CYP1A2 enzyme activity in liver, lung and skin. Toxicol. Appl. Pharmacol. 130, 197–208; DeVito, M.J., Menache, G., Diliberto, J.J., Ross, D.G., Birnbaum L.S., 2000. Dose–response relationships for induction of CYP1A1 and CYP1A2 enzyme activity in liver, lung, and skin in female mice following subchronic exposure to polychlorinated biphenyls. Toxicol. Appl. Pharmacol. 167, 157–172] Female mice received 0, 1.5, 15, 150 or 450 ng TCDD/kg/day or approximately 0, 1.5, 15, 150 or 450 ng TEQ/kg/day of MIX-1 or MIX-2 by gavage 5 days per week for 13 weeks. Mice were immunized 3 days after the last exposure and 4 days later, body, spleen, thymus, and liver weights were measured, and antibody response to SRBCs was observed. Exposure to TCDD, MIX-1, and MIX-2 suppressed the antibody response in a dose-dependent manner. Two-way ANOVA indicated no differences in the response between TCDD and the mixtures for body weight, spleen/body weight and decreased antibody responses. The results support the use of the TEF methodology and suggest that immune suppression by dioxin-like chemicals may be of concern at or near background human exposures.

Effect of In Ovo Exposure to an Organochlorine Mixture Extracted from Double Crested Cormorant Eggs (Phalacrocorax auritus) and PCB 126 on Immune Function of Juvenile Chickens

Organochlorine (OC) contaminants including polychlorinated biphenyls (PCBs) and p, p'-dichlorodiphenyldichloroethylene (DDE) have been associated with immune modulation in wild fish-eating birds from the Great Lakes. The objective of this study was to evaluate the immune function of juvenile chickens after in ovo exposure to PCB 126 or an environmentally relevant OC mixture extracted from eggs of double crested cormorants (Phalacrocorax auritus) from Green Bay, Lake Michigan, USA. Fertile white leghorn chicken (Gallus domesticus) eggs were injected before incubation with 0.55-1.79 ng TCDD equivalents (TEQ)/egg PCB 126 and 1.2-4.9 ng TEQs/egg of cormorant egg extract into the air cell in two separate experiments. After hatching, the immune function was tested using in vivo phytohemagglutinin (PHA) skin response in 11-day-old chicks, antibody titers to immunization with sheep red blood cells (SRBC) in 28-day-old chicks, and, at necropsy, thymus and bursal mass and cellularity. PCB 126 decreased antibody titers at all doses and decreased the thymus and bursa index but not cellularity at 1.79 ng TEQ/egg. The cormorant egg extract caused no significant alterations in immune function even though it has been demonstrated as immunotoxic in chicken embryos. However, twofold to threefold increases in total anti-SRBC titers in 28-day-old chicks exposed to 1.2 or 2.4 ng TEQ/egg of cormorant extract were similar to elevations in anti-SRBC titer observed in Caspian tern (Sterna caspia) chicks from a highly OC-contaminated site in Saginaw Bay, Lake Huron. Posthatch exposure to OC through fish consumption in addition to in ovo OC exposure might be associated with the immune modulation reported in wild birds. Chicks in this study might have begun to compensate for embryonic immunotoxicity by the ages at which we studied them.

Levels and congener distributions of PCDDs, PCDFs and dioxin-like PCBs in environmental and human samples: a review

The term “dioxins” is often used in a confusing way. In toxicological considerations—and also in the present report—the term is used to designate the PCDDs, the PCDFs and the coplanar (“dioxin-like”) PCBs, since these classes of compounds show the same type of toxicity. Because of the large number of congeners, relevant individual congeners are assigned with a toxic equivalency factor (TEF) that relate their toxicity to that of tetrachlorodibenzo-p-dioxin (TCDD) (2,3,7,8-TCDD) and are to be evaluated as dioxins. Each concentration of an individual congener in a mixture is multiplied with its TEF, and the resulting TCDD equivalents are added up and expressed as WHO-endorsed toxic equivalents (WHO-TEQ). Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are mainly the by-products of industrial processes (such as metallurgical processing, bleaching of paper pulp, and the manufacturing of some herbicides and pesticides) but they can also result from natural processes like volcanic eruptions and forest fires. Waste incineration, particularly if combustion is incomplete, is among the largest contributors to the release of PCDDs and PCDFs into the environment. Due to their persistence, PCDDs, PCDFs and PCBs are part of the so-called persistent organic pollutants group of compounds that also include some chlorinated pesticides. Since they have a high lipophilicity and resist transformation, they bio-accumulate in animal and human adipose tissues. Consumption of food is considered as the major source of non-occupational human exposure to PCDD/Fs with foodstuffs from animal origin accounting for more than 90% of the human body burden. With meat, dairy, and fish products being the main contributors. The aim of the present review was to summarize experimental data regarding dioxin emissions from contaminated and uncontaminated biological and environmental samples, from the available literature. The information will be presented chronologically with respect to distribution in human milk, serum; food, water, air, soils and sediments.

Exposure and Multiple Lines of Evidence Assessment of Risk for PCBs Found in the Diets of Passerine Birds at the Kalamazoo River Superfund Site, Michigan

ABSTRACT Dietary exposures of passerine birds at the Kalamazoo River, Michigan, were examined due to the presence of polychlorinated biphenyls (PCBs) in the terrestrial and aquatic food webs. Average potential daily doses in diets were 6- to 29-fold and 16- to 35-fold greater at a contaminated location than at a reference location for PCB exposures quantified as total PCBs and 2,3,7,8–tetrachlorodibenzo-p-dioxin equivalents (TEQs), respectively. Birds with diets comprised of primarily aquatic insects had greater dietary exposure than birds with diets of primarily terrestrial insects. Risk associated with dietary exposure varied with the selection of the threshold for effects including hazard quotients, which exceeded 1 in instances where the most conservative toxicity reference values were utilized. Risk based on concentrations of PCBs in the tissues indicated little risk to avian species, and co-located studies evaluating reproductive health did not suggest that observed incidences of diminished reproductive success were related to PCB exposure. Measures of risk based on comparison to toxicity reference values (TRVs) were consistent with direct measures of ecologically relevant endpoints of reproductive fitness, but uncertainty exists in the selection of threshold values for effects in these species especially based on TEQs. This is largely due to the absence of species-specific, dose-response relationships. Therefore, the best estimate of risk is through the application of multiple lines of evidence.

Productivity of Tree Swallows (Tachycineta bicolor) Exposed to PCBs at the Kalamazoo River Superfund Site

A 123-km stretch of the Kalamazoo River in Michigan, was designated a Superfund site in 1990 due to historical releases of effluent containing polychlorinated biphenyl (PCB)-contaminated paper waste. Risk to bird species in the river ecosystem was evaluated using the tree swallow (Tachycineta bicolor) as a monitor for possible effects due to PCB exposure at two nesting locations, one in the Superfund site and one in an upstream reference location that is less contaminated with PCBs. In 2 of the 3 years of the study, clutch size at the contaminated location was 3.7 ± 1.4 and 4.8 ± 0.73 eggs per nest (mean ± SD), which was significantly less than the clutch size at the reference location (5.0 ± 1.1 and 5.3 ± 1.1 eggs per nest). However, there were no statistically significant differences in fledging success, predicted brood size, predicted number of fledglings, or growth of nestlings between the Kalamazoo River Superfund site and an upstream reference location with lesser concentrations of PCBs in the sediments and riparian soils. Productivity and hatching success comparisons between these same sites were also not significantly different; however, the power of these conclusions was less (p < .10). The reduction in clutch size at the co-contaminated location could not be attributed to PCBs due to a number of confounding factors, including Co-cocontaminants, habitat structure, and food availability. Other reproductive parameters were not significantly impaired, and the size of the newly established colony at the Kalamazoo River Superfund site continued to grow over the period of the study. These site-specific observations, combined with multiple lines of evidence approach that considered results reported for the effects of both total PCBs and 2,3,7,8 tetrachlorodibenzo-p-dioxin equivalents (TEQ) on tree swallows at other locations, suggest that there were no significant population-level effects of PCBs on tree swallows at the Kalamazoo River Superfund site.

Identification of Ah Receptor Agonists in Sediment of Meiliang Bay, Taihu Lake, China

Deterioration of ecosystem and water quality in Taihu Lake, the third largest freshwater lake in China, is of great concern in China. However, most evaluations on water and sediment were carried out by chemical analysis, which could hardly gain information on the risk stressors affecting the system. Sediment samples from Meiliang Bay, Taihu Lake were assayed for AhR-mediated EROD induction using a rat hepatoma cell line (H4IIE). The known AhR agonists including PCDD/Fs, PCBs, and PAHs were analyzed by instruments. The cause-effect relationship between the observed EROD activity and chemical concentrations of AhR agonists and their dose-effect relationship were examined. Our results showed that sediment extracts could induce significant AhR effects, and the chemical-derived TCDD equivalents (TEQ(cal)) were significantly correlated to bioassay-derived TCDD equivalents (TEQ(bio)) (R = 0.85, p < 0.01). Among different contributors, PAHs could account for 70-93% and PCDD/Fs could contribute less than 30% of TEQ(cal). PCBs exhibited almost no contribution. Therefore, integration of EROD bioassay and chemical analysis provided an effective way for identifying the potential risk stressors. Underthis circumstance, a quantitative dose--effect relationship between TEQ(PAH) and EROD activity could be established, suggesting that the observed AhR effect was mostly derived from PAHs. The implication is that the EROD assay and the identified risk stressors (PAHs) may be used in lieu of detailed environmental analysis to follow the progression of a remediation strategy.

Carcinogenicity of “Non-Dioxinlike” Polychlorinated Biphenyls

Complex technical mixtures of polychlorinated biphenyls (PCBs) cause liver and thyroid neoplasms in rodents, whereas very few data are available on the carcinogenic potency of single non-dioxinlike (NDL) PCB congeners. In most genotoxicity assays technical PCB mixtures and individual congeners were inactive, suggesting that PCBs act as indirect, nongenotoxic carcinogens. Various mechanisms, including suppression of apoptosis in preneoplastic cells or inhibition of intercellular communication, have been suggested to be active in liver tumor promotion by PCBs. A decrease in thyroid hormone levels after PCB treatment has been suggested to play a role in the development of thyroid neoplasms in rats; however, other mechanisms may also be involved. Results from a chronic carcinogenicity study in rats indicate that not the dose of total PCBs but the total TCDD or toxic equivalents (TEQs) associated with “dioxinlike” (DL) constituents within a technical mixture are mainly if not exclusively responsible for the development of liver neoplasms in female rats. Quantitative comparison reveals almost identical dose-response curves for the total TEQs in various technical PCB mixtures and for TCDD as inducers of hepatic neoplasms in female rats. Tumor promotion experiments have shown, however, that, after initiation with a genotoxic carcinogen, technical PCB mixtures and individual DL-and NDL-PCBs act as liver tumor promoters in rodents. Based on these data, a weak carcinogenic potency of individual NDL-PCB congeners cannot be excluded. In epidemiological studies, increased mortality from cancers of the liver, gallbladder, biliary tract, gastrointestinal tract, and from brain cancer and malignant melanoma were observed in workers exposed to a series of technical PCB mixtures. A significant association between PCB concentrations in adipose tissue and non-Hodgkins lymphoma was found in another study. While in all human studies mixed exposure to DL-and NDL-PCBs occurred, no comprehensive data are available on the relative contribution of NDL-PCBs to the overall external and/or internal PCB exposure in those cohorts.

AhR-active compounds in sediments of the Haihe and Dagu Rivers, China

Total concentrations of compounds that can cause activation of the aryl hydrocarbon receptor (AhR) in extracts of river sediments from various locations in the Haihe and Dagu Rivers, Tianjin, China were determined by use of the in vitro H4IIE- luc cell line. AhR-active compounds were isolated from sediments by Soxhlet extraction, and the crude extracts were fractionated using a Florisil column into three Fractions. The response of samples was compared to the TCDD standard and expressed as 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) equivalents (TCDD-EQs). Significant dioxin-like activity was observed in each sample. The TCDD-EQs in crude extracts of sediments (SCEs), as determined with the bioassay were 2–4 times greater than the sum of the TCDD-EQs of the eluent from fractions separated with a Florisil column. The results also showed that Fractions 2 and 3 contained most of the AhR-mediated activity. The results obtained by using the bioassay were compared with those of previous measurements of the concentrations of polychlorinated dibenzo- p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) and the structurally-similar AhR-active polychlorinated biphenyls (PCBs). It was determined that sediments from the Dagu River contained greater concentrations of TCDD-EQ than did sediments from the Haihe River except at Jingangqiao (location R3), which is associated with industrial activities in the adjacent densely populated area. The concentrations of TCDD-EQs, based on the EC 20 and the relative potency ranges, of SCEs ranged from 330 to 930 and 1200 to 13 900 pg TCDD-EQ g −1 dry wt in Haihe and Dagu Rivers, respectively.