PCDD/Fs, PBDD/Fs, and PBDEs in the air of an e-waste recycling area (Taizhou) in China: current levels, composition profiles, and potential cancer risks.

Atmospheric concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) were measured in Taizhou, a large electronic equipment waste (e-waste) recycling area in East China. The mean concentrations (in summer and winter) of PCDD/Fs (0.45 and 0.39 pg WHO-TEQ m⁻³, where WHO-TEQ is the toxic equivalent set by the World Health Organisation), PBDD/Fs (0.22 and 0.18 pg WHO-TEQ m⁻³), and PBDEs (270 and 225 pg m⁻³) in this region have declined compared with those in 2005, due to regulations on primitive e-waste recycling activities. However, these concentrations remain higher than the historically highest levels in Europe and North America. The congener profiles of 2,3,7,8-substituted PCDD/Fs were similar, with OCDD, 1,2,3,4,6,7,8-HpCDF, OCDF, and 1,2,3,4,6,7,8-HpCDD being the most abundant congeners at all sites. The PCDD/F homologue profiles in the present study were different from those typically observed at non-e-waste locations, indicating a distinct source in this region. Seasonal differences were found in the lower brominated PBDE profiles. These differences indicate that the PBDE emission sources in summer (e.g., strong evaporation sources) differed from those in winter. However, the relatively steady congener profiles of the highly brominated PBDEs suggest that these PBDEs were controlled primarily by similar emission mechanisms. The lifetime excess cancer risks from exposure to PCDD/Fs and PBDD/Fs via inhalation ranged from 0.7 × 10⁻5 to 5.4 × 10⁻5, or approximately 80 cancer cases in the Taizhou population.

Thiol-activated DNA damage by α-bromo-2-cyclopentenone.

Some biologically active chemicals are relatively stable in the extracellular environment but, upon entering the cell, undergo biotransformation into reactive intermediates that covalently modify DNA. The diverse chemical reactions involved in the bioactivation of DNA-damaging agents are both fundamentally interesting and of practical importance in medicinal chemistry and toxicology. The work described here examines the bioactivation of α-haloacrolyl-containing molecules. The α-haloacrolyl moiety is found in a variety of cytotoxic natural products including clionastatin B, bromovulone III, discorahabdins A, B, and C, and trichodenone C, in mutagens such as 2-bromoacrolein and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), and in the anticancer drug candidates brostallicin and PNU-151807. Using α-bromo-2-cyclopentenone (1) as a model compound, the activation of α-haloacrolyl-containing molecules by biological thiols was explored. The results indicate that both low molecular weight and peptide thiols readily undergo conjugate addition to 1. The resulting products are consistent with a mechanism in which initial addition of thiols to 1 is followed by intramolecular displacement of bromide to yield a DNA-alkylating episulfonium ion intermediate. The reaction of thiol-activated 1 with DNA produces labile lesions at deoxyguanosine residues. The sequence specificity and salt dependence of this process is consistent with involvement of an episulfonium ion intermediate. The alkylated guanine residue resulting from the thiol-triggered reaction of 1 with duplex DNA was characterized using mass spectrometry. The results provide new insight regarding the mechanisms by which thiols can bioactivate small molecules and offer a more complete understanding of the molecular mechanisms underlying the biological activity of cytotoxic, mutagenic, and medicinal compounds containing the α-haloacrolyl group.

Dioxin-like activity in Japanese indoor dusts evaluated by means of in vitro bioassay and instrumental analysis: brominated dibenzofurans are an important contributor.

In our previous study, we demonstrated that dioxin-like activity in sulfuric-acid-treated extracts of Japanese indoor dust was higher than the activity in contaminated sediments. In the current study, we used high-performance liquid chromatography (HPLC) fractionation in combination with the dioxin-responsive chemical-activated luciferase gene expression (DR-CALUX) assay and gas chromatography-high-resolution mass spectrometry (GC-HRMS) to quantitatively evaluate dioxin-like compounds in indoor dusts. Selected four sulfuric-acid-treated extracts of indoor dusts were fractionated into seven fractions by means of HPLC with a nitrophenylpropylsilica column, and the activity in the first fraction of each extract was much higher than the activities in the other fractions. Therefore, each of the first fractions was further fractionated into 90 fractions by HPLC with an octadecylsilica column, and all the fractions were analyzed by means of the DR-CALUX assay. On the basis of elution characteristics, the active compounds in the fractions showing high activity were determined to be polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), coplanar polychlorinated biphenyls (Co-PCBs), and polychlorinated naphthalenes (PCNs), or supposed to be polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs). These compounds in the 33 dusts extracts were quantified by means of GC-HRMS, and their median-based contributions of the theoretical CALUX-TEQs [2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) equivalent] chemically calculated for PBDFs, PCDDs, PCDFs, non-ortho Co-PCBs, PCNs, and mono-ortho Co-PCBs to the experimental values (38-1400 pg/g, median 160 pg/g) were 17%, 14%, 8.8%, 0.98%, 0.10%, and 0.019%, respectively. Our results indicate that PBDFs, which are not internationally regulated dioxins, were important contributors to dioxin-like activity in Japanese dust and that further analysis of PBDFs in indoor dust is required so that the risk of exposure to these compounds via dust can be assessed.

Indoor contamination with hexabromocyclododecanes, polybrominated diphenyl ethers, and perfluoroalkyl compounds: an important exposure pathway for people?

This review underlines the importance of indoor contamination as a pathway of human exposure to hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs), and perfluoroalkyl compounds (PFCs). There is ample evidence of substantial contamination of indoor dust with these chemicals and that their concentrations in indoor air exceed substantially those outdoors. Studies examining the relationship between body burden and exposure via indoor dust are inconsistent; while some indicate a link between body burdens and PBDE and HBCD exposure via dust ingestion, others find no correlation. Likewise, while concentrations in indoor dust and human tissues are both highly skewed, this does not necessarily imply causality. Evidence suggests exposure via dust ingestion is higher for toddlers than adults. Research priorities include identifying means of reducing indoor concentrations and indoor monitoring methods that provide the most "biologically-relevant" measures of exposure as well as monitoring a wider range of microenvironment categories. Other gaps include studies to improve understanding of the following: emission rates and mechanisms via which these contaminants migrate from products into indoor air and dust; relationships between indoor exposures and human body burdens; relevant physicochemical properties; the gastrointestinal uptake by humans of these chemicals from indoor dust; and human dust ingestion rates.

Spatial trends and associated biological responses of organochlorines and brominated flame retardants in hatchlings of north Atlantic kittiwakes (Rissa tridactyla).

Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), some organochlorinated pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and hexabromocyclododecane (HBCD), were analyzed in yolk sacs of kittiwake (Rissa tridactyla) hatchlings from Kongsfjorden at Svalbard (Norwegian Arctic; 79 degrees N) and from Runde, an island on the coast of Norway (62 degrees N). Retinol (vitamin A), retinyl palmitate, and alpha-tocopherol (vitamin E) were measured in plasma and liver of the hatchlings to examine whether these vitamins were associated with the POPs. Higher levels of PCBs and OCPs were found in hatchlings from Kongsfjorden than in hatchlings from Runde. However, HBCD levels were significantly lower in hatchlings from Kongsfjorden compared to those in hatchlings from Runde. No differences between the two populations of kittiwake hatchlings were found regarding levels of PBDEs. In comparison with seabirds from other European waters and the Canadian Arctic, the kittiwakes seemed to have relatively high levels of PBDEs and HBCD. No effects on morphological variables or vitamin levels by the POPs were revealed, but multivariate regression indicated that liver tocopherol levels may be influenced by POPs.

Brominated indoles and phenols in marine sediment and water extracts from the north and baltic seas-concentrations and effects.

This work presents results from analytical as well as ecotoxicologic investigations of sediment and water samples from the North and Baltic Seas. A bioassay-directed procedure was used to investigate cause-effect relationships between observed effects in acute laboratory bioassays (luminescent bacteria assay with Vibrio fischeri and embryo test with Danio rerio) and analyte concentrations in extracted samples. Brominated phenols and indoles-including 4-bromophenol; 2,4-dibromophenol; 4- and 6-bromoindole; 3,4-, 4,6-, and 3,6-dibromoindole; and tribrominated compounds-were identified in partly remarkable concentrations (up to 40,000 ng g(-1) total organic carbon TOC for 4-bromophenol) in North Sea sediment samples and water samples (913 ng L(-1) 3,6-dibromoindole) from the German Bight. The toxicity of some of the identified brominated substances was low, with median effect concentration levels (EC(50)) ranging from 0.08 to 21.7 mg/L for V. fischeri and 4.3 to 46.3 mg/L for D. rerio. Comparison of the concentrations of analytes with ECs showed a toxicity contribution of brominated phenols and indoles to overall toxicity of the fraction. In the case of one water sample from the German Bight, brominated phenols and indoles accounted for the observed toxicity. Brominated phenols and indoles, which are assumed to be of biogenic origin, have rarely been discussed so far in the context of ecotoxicologic effects in marine ecosystems.

Analysis of Ah receptor pathway activation by brominated flame retardants.

Brominated flame-retardants (BFRs) are used as additives in plastics to decrease the rate of combustion of these materials, leading to greater consumer safety. As the use of plastics has increased, the production and use of flame-retardants has also grown. Many BFRs are persistent and have been detected in environmental samples, raising concerns about the biological/toxicological risk associated with their use. Most BFRs appear to be non-toxic, however there is still some concern that these compounds, or possible contaminants in BFRs mixtures could interact with cellular receptors. In this study we have examined the interaction of decabromodiphenyl ether, Firemaster BP4A (tetrabromobisphenol A), Firemaster PHT4 (tetrabromophthalic anhydride), hexabromobenzene, pentabromotoluene, decabromobiphenyl, Firemaster BP-6 (2,2',4,4',5,5'-hexabromobiphenyl) and possible contaminants of BFR mixtures with the Ah receptor. Receptor binding and activation was examined using the Gel Retardation Assay and increased expression of dioxin responsive genes was detected using the reporter gene based CALUX assay. The results demonstrate the ability of BFRs to activate the AhR signal transduction pathway at moderate to high concentrations as assessed using both assays. AhR-dependent activation by BFRs may be due in part to contaminants present in commercial/technical mixtures. This was suggested by our comparative analysis of Firemaster BP-6 versus its primary component 2,2',4,4',5,5'-hexabromobiphenyl. Some technical mixtures of brominated flame-retardants contain brominated biphenyls, dioxins or dibenzofurans as contaminants. When tested in the CALUX assay these compounds were found to be equivalent to, or more active than their chlorinated analogues. Relative effective potency values were determined from dose response curves for these brominated HAHs.

Structure-activity relationship for bromoindole carbaldehydes: effects on the sea urchin embryo cell cycle.

Natural derivatives of indole-3-carbaldehyde were isolated from the tropical marine ascidian Stomoza murravi. A series of 13 derivatives, three natural and 10 synthetic (brominated and N-methylated), were examined for their effects on cell division of sea urchin eggs. These derivatives were shown to inhibit the first mitotic cycle in a concentration-dependent manner. By comparing the IC50 values with the structure of the various molecules, we were able to determine that bromination increased the cytotoxicity of the compound with a maximum occurring when bromine was added to carbon number 2, while addition of N-methylation was shown to markedly reduce the cytotoxicity of these same compounds brominated at carbon 2 only. Biological activity of this family of compounds has been characterized, via detailed study of addition of the most active derivative, 2,5,6-tribromoindole-3-carbaldehyde, on macromolecule synthesis and cytoskeleton reorganization during the first mitotic cycle of fertilized sea urchin eggs. Fluorescence localization of chromatin and microtubules revealed that 2,5,6-tribromoindole-3-carbaldehyde allowed pronuclei migration and fusion but prevented the condensation of chromatin, nuclear envelope breakdown, and bipolar mitotic spindle assembly, inducing an arrest of sea urchin embryogenesis at the beginning of mitosis. It is postulated here that this phenotype is likely to be due to a strong inhibition of DNA replication and protein synthesis.