Nontarget Screening of Organohalogen Compounds in the Liver of Wild Birds from Osaka, Japan: Specific Accumulation of Highly Chlorinated POP Homologues in Raptors.

Nontarget screening studies have recently revealed the accumulation of typically unmonitored organohalogen compounds (OHCs) in various marine animals, but information for terrestrial food chains is still lacking. This study investigated the accumulation profiles of known and unknown OHCs in the liver of representative wild bird specimens from Osaka, Japan using nontarget analysis based on two-dimensional gas chromatography-time-of-flight mass spectrometry. A large number of unmonitored OHCs were identified, including anthropogenic contaminants and marine halogenated natural products (HNPs), and their accumulation profiles were considered to be influenced by terrestrial and brackish water-based diets. Anthropogenic OHCs were highly accumulated in terrestrial predator species (peregrine falcon, hawks, and black kite), and some unmonitored highly chlorinated contaminants reached the levels of microgram per gram lipid in the liver, i.e., C10-/C15-based chlordane related compounds (CHLs) and their epoxides, dichlorodiphenyldichloroethylene (DDE) homologues, and polychlorinated terphenyls (PCTs). In contrast, HNPs were accumulated at higher levels in piscivorous birds (gray heron and common cormorant). Considering the enrichment of the unmonitored C10-/C15-based CHLs, PCTs, and DDE homologues relative to structurally similar persistent organic pollutants (POPs) in high trophic-level species such as raptors, further studies are needed to elucidate their environmental levels, behavior in terrestrial food chains, and ecotoxicological impacts.

Mother to Fetus Transfer of Hydroxylated Polychlorinated Biphenyl Congeners (OH-PCBs) in the Japanese Macaque (Macaca fuscata): Extrapolation of Exposure Scenarios to Humans.

Prenatal hydroxylated polychlorinated biphenyls (OH-PCBs) exposure may disrupt fetal brain development during the critical period of thyroid hormone (TH) action. However, there are limited studies on the OH-PCB transfer to the fetal brain, particularly in primates. In this study, we selected the Japanese macaque (Macaca fuscata) as a model animal for the fetal transfer of OH-PCBs in humans and revealed OH-PCB concentrations and their relationships in maternal and fetal blood, liver, and brain. l-thyroxine (T4)-like OH-PCBs including 4OH-CB187, a major congener in humans, were found in high proportions in the blood, liver, brain, and placenta of pregnant Japanese macaques. OH-PCBs were detected in the fetal brain and liver in the first trimester, indicating their transfer to the brain in the early pregnancy stage. 4OH-CB187 and 4OH-CB202 were the major congeners found in fetal brain, indicating that these T4-like OH-PCBs are transported from maternal blood to the fetal brain via the placenta. These results indicate that further studies are needed on the effects of OH-PCBs on the developing fetal brain.

Nontarget and Target Screening of Organohalogen Compounds in Mussels and Sediment from Hiroshima Bay, Japan: Occurrence of Novel Bioaccumulative Substances.

Recent screening surveys have shown the presence of unknown halogenated compounds in the marine environment at comparable levels to persistent organic pollutants (POPs). However, their exposure levels and profiles in marine organisms and bioaccumulative potentials remain unclear. The present study performed nontarget/target screening of organohalogen compounds (OHCs) in mussel and sediment samples collected from Hiroshima Bay, Japan, in 2012 and 2018 by using integrated analyses of two-dimensional gas chromatography-high resolution time-of-flight mass spectrometry (GC×GC-HRToFMS) and magnetic sector GC-HRMS. Nontarget analysis by GC×GC-HRToFMS revealed the detection of approximately 60 OHCs including unknown mixed halogenated compounds (UHC-Br3-5Cl) with molecular formulae of C9H6Br3ClO, C9H5Br4ClO, and C9H4Br5ClO in the mussel. Interestingly, UHC-Br3-5Cl concentrations in the mussel samples, which were semi-quantified by GC-HRMS, were comparable to or higher than those of POPs at all the locations surveyed, and their geographical distribution patterns differed from those of other OHCs. These results suggest that UHC-Br3-5Cl are ubiquitous in coastal waters of Hiroshima Bay and derived from a specific source(s). The biota-sediment accumulation factors (BSAFs) of UHC-Br3-5Cl, estimated for a paired sample set of mussel (ng/g lw) and sediment (ng/g TOC), were 1 order of magnitude higher than those for POPs with similar log Kow values, indicating their high bioaccumulative potential.

Targeted metabolome analysis of the dog brain exposed to PCBs suggests inhibition of oxidative phosphorylation by hydroxylated PCBs.

Canis lupus familiaris (domestic dog) possess a high capacity to metabolize higher-chlorinated polychlorinated biphenyls (PCBs) to thyroid hormone (TH)-like hydroxylated PCB metabolites (OH-PCBs). As a result, the brain could be at high risk of toxicity caused by OH-PCBs. To evaluate the effect of OH-PCBs on dog brain, we analyzed OH-PCB levels in the brain and the metabolome of the frontal cortex following exposure to a mixture of PCBs (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187, and 202). 4-OH-CB202 and 4-OH-CB107 were major OH-PCBs in the brain of PCB-exposed dogs. These OH-PCBs were associated with metabolites involved in urea cycle, proline-related compounds, and purine, pyrimidine, glutathione, and amino-acid metabolism in dog brain. Moreover, adenosine triphosphate levels in the PCBs exposure group were significantly lower than in the control group. These results suggest that OH-PCB exposure is associated with a disruption in TH homeostasis, generation of reactive oxygen species, and/or disruption of oxidative phosphorylation (OXPHOS) in brain cells. Among them, OXPHOS disturbance could be associated with both disruptions in cellular amino-acid metabolism and urea cycle. Therefore, an OXPHOS activity assay was performed to evaluate the disruption of OXPHOS by OH-PCBs. The results indicated that 4-OH-CB107 inhibits the function of Complexes III, IV, and V of the electron transport chain, suggesting that 4-OH-CB107 inhibit these complexes in OXPHOS. The neurotoxic effects of PCB exposure may be mediated through mitochondrial toxicity of OH-PCBs in the brain.

Complex Mixtures of Brominated/Chlorinated Diphenyl Ethers and Dibenzofurans in Soils from the Agbogbloshie e-Waste Site (Ghana): Occurrence, Formation, and Exposure Implications.

The distribution and toxic equivalents (TEQs) of brominated and chlorinated dibenzo- p-dioxins/dibenzofurans (PBDD/Fs and PCDD/Fs) in soils from Agbogbloshie e-waste site (Ghana) were investigated. The composition of brominated/chlorinated dibenzofurans (PXDFs) and diphenyl ethers (PBDEs, PCDEs, and PXDEs) was examined using two-dimensional gas chromatography-time-of-flight mass spectrometry to elucidate possible formation pathways of dioxins from e-waste recycling. The highest concentrations of PCDD/Fs and PBDD/Fs were found, respectively, in the open burning (1.3-380 ng/g dry weight) and dismantling areas (11-1000 ng/g dry weight) and were comparable to the highest reported for informal e-waste sites. PXDFs and PXDEs were detected at up to the range of hundreds of nanograms per gram. The homologue profiles suggest that PXDFs were formed mainly from PBDFs through successive Br-to-Cl exchange. However, monobromo-PCDFs were also derived from de-novo-generated PCDFs in open burning areas. PBDFs contributed similar or higher TEQs (7.9-5400 pg/g dry weight) compared with PCDD/Fs (6.8-5200 pg/g dry weight), whereas PXDFs were also substantial TEQ contributors in open burning areas. The high TEQs of PBDFs in the dismantling area (120-5200 pg/g dry weight) indicate the need to consider brominated dioxins besides chlorinated dioxins in future studies on health implications for e-waste workers and local residents.

Uptake and Metabolism of Human Pharmaceuticals by Fish: A Case Study with the Opioid Analgesic Tramadol.

Recent species-extrapolation approaches to the prediction of the potential effects of pharmaceuticals present in the environment on wild fish are based on the assumption that pharmacokinetics and metabolism in humans and fish are comparable. To test this hypothesis, we exposed fathead minnows to the opiate pro-drug tramadol and examined uptake from the water into the blood and brain and the metabolism of the drug into its main metabolites. We found that plasma concentrations could be predicted reasonably accurately based on the lipophilicity of the drug once the pH of the water was taken into account. The concentrations of the drug and its main metabolites were higher in the brain than in the plasma, and the observed brain and plasma concentration ratios were within the range of values reported in mammalian species. This fish species was able to metabolize the pro-drug tramadol into the highly active metabolite O-desmethyl tramadol and the inactive metabolite N-desmethyl tramadol in a similar manner to that of mammals. However, we found that concentration ratios of O-desmethyl tramadol to tramadol were lower in the fish than values in most humans administered the drug. Our pharmacokinetic data of tramadol in fish help bridge the gap between widely available mammalian pharmacological data and potential effects on aquatic organisms and highlight the importance of understanding drug uptake and metabolism in fish to enable the full implementation of predictive toxicology approaches.

Anthropogenic and Naturally Produced Brominated Phenols in Pet Blood and Pet Food in Japan.

Present study determined concentrations and residue patterns of bromophenols (BPhs) in whole blood samples of pet cats and pet dogs collected from veterinary hospitals in Japan. BPhs concentrations were higher in cat blood than in dog blood, with statistically insignificant differences (p = 0.07). Among the congeners, 2,4,6-tribromophenol (TBPh) constituted the majority of BPhs (>90%) detected in both species. Analysis of commercial pet food to estimate exposure routes showed that the most abundant congener in all pet food samples was 2,4,6-TBPh, accounting for >99% of total BPhs. This profile is quite similar to the blood samples of the pets, suggesting that diet might be an important exposure route for BPhs in pets. After incubation in polybrominated diphenyl ether (PBDE) mixtures (BDE-47, BDE-99 and BDE-209), 2,4,5-TBPh was found in dog liver microsomes but not in cat liver microsomes, implying species-specific metabolic capacities for PBDEs. Formation of 2,4,5-TBPh occurred by hydroxylation at the 1' carbon atom of the ether bond of BDE-99 is similar to human study reported previously. Hydroxylated PBDEs were not detected in cats or dogs; therefore, diphenyl ether bond cleavage of PBDEs can also be an important metabolic pathway for BPhs formation in cats and dogs.

Occurrence of Natural Mixed Halogenated Dibenzo-p-Dioxins: Specific Distribution and Profiles in Mussels from Seto Inland Sea, Japan.

In addition to unintentional formation of polychlorinated (PCDD/Fs), polybrominated (PBDD/Fs), and mixed halogenated (PXDD/Fs) dibenzo-p-dioxins/dibenzofurans during industrial activities, recent studies have shown that several PBDD and PXDD congeners can be produced by marine algal species from the coastal environment. However, multiple exposure status of anthropogenic and naturally derived dioxins in marine organisms remains unclear. The present study examined the occurrence, geographical distribution, and potential sources of PCDD/Fs, PBDD/Fs, and PXDD/Fs using mussels and brown algae collected in 2012 from Seto Inland Sea, Japan. The results showed the widespread occurrence of not only PCDD/Fs but also PBDDs and PXDDs in Seto Inland Sea. The geographical distribution pattern of PBDDs was similar to that of PXDDs, which were obviously different from that of PCDDs and PCDFs, and a significant positive correlation was observed between the levels of their predominant congeners, i.e., 1,3,7-/1,3,8-TrBDDs and DiBMoCDDs. Interestingly, potential precursors of 1,3,7-/1,3,8-TrBDDs and DiBMoCDDs, hydroxylated tetrabrominated diphenyl ethers (6-HO-BDE-47 and 2'-HO-BDE-68) and their mixed halogenated analogue (HO-TrBMoCDE), were also identified in the mussel and brown alga samples collected at the same site, by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC-ToFMS) analyses. It is noteworthy that residue levels of 1,3,7-/1,3,8-TrBDDs and DiBMoCDDs in the mussel were 30 times higher than those in the brown alga, suggesting the bioaccumulation of these natural dioxins.

Species- and Tissue-Specific Profiles of Polybrominated Diphenyl Ethers and Their Hydroxylated and Methoxylated Derivatives in Cats and Dogs.

The adverse effects of elevated polybrominated diphenyl ether (PBDE) levels, reported in the blood of domestic dogs and cats, are considered to be of great concern. However, the tissue distribution of PBDEs and their derivatives in these animals is poorly understood. This study determined the concentrations and profiles of PBDEs, hydroxylated PBDEs (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs), and 2,4,6-tribromophenol (2,4,6-tri-BPh) in the blood, livers, bile, and brains of dogs and cats in Japan. Higher tissue concentrations of PBDEs were found in cats, with the dominant congener being BDE209. BDE207 was also predominant in cat tissues, indicating that BDE207 was formed via BDE209 debromination. BDE47 was the dominant congener in dog bile, implying a species-specific excretory capacity of the liver. OH-PBDE and MeO-PBDE concentrations were several orders of magnitude higher in cat tissues, with the dominant congener being 6OH-BDE47, possibly owing to their intake of naturally occurring MeO-PBDEs in food, MeO-PBDE demethylation in the liver, and lack of UDP-glucuronosyltransferase, UGT1A6. Relatively high concentrations of BDE209, BDE207, 6OH-BDE47, 2'MeO-BDE68, and 2,4,6-tri-BPh were found in cat brains, suggesting a passage through the blood-brain barrier. Thus, cats in Japan might be at a high risk from PBDEs and their derivatives, particularly BDE209 and 6OH-BDE47.

Organohalogen Compounds in Pet Dog and Cat: Do Pets Biotransform Natural Brominated Products in Food to Harmful Hydroxlated Substances?

There are growing concerns about the increase in hyperthyroidism in pet cats due to exposure to organohalogen contaminants and their hydroxylated metabolites. This study investigated the blood contaminants polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PCBs, OH-PBDEs, and MeO-PBDEs), in pet dogs and cats. We also measured the residue levels of these compounds in commercially available pet foods. Chemical analyses of PCBs and OH-PCBs showed that the OH-PCB levels were 1 to 2 orders of magnitude lower in cat and dog food products than in their blood, suggesting that the origin of OH-PCBs in pet dogs and cats is PCBs ingested with their food. The major congeners of OH-/MeO-PBDEs identified in both pet food products and blood were natural products (6OH-/MeO-BDE47 and 2'OH-/MeO-BDE68) from marine organisms. In particular, higher concentrations of 6OH-BDE47 than 2'OH-BDE68 and two MeO-PBDE congeners were observed in the cat blood, although MeO-BDEs were dominant in cat foods, suggesting the efficient biotransformation of 6OH-BDE47 from 6MeO-BDE47 in cats. We performed in vitro demethylation experiments to confirm the biotransformation of MeO-PBDEs to OH-PBDEs using liver microsomes. The results showed that 6MeO-BDE47 and 2'MeO-BDE68 were demethylated to 6OH-BDE47 and 2'OH-BDE68 in both animals, whereas no hydroxylated metabolite from BDE47 was detected. The present study suggests that pet cats are exposed to MeO-PBDEs through cat food products containing fish flavors and that the OH-PBDEs in cat blood are derived from the CYP-dependent demethylation of naturally occurring MeO-PBDE congeners, not from the hydroxylation of PBDEs.

Association of XRCC1 polymorphisms with arsenic methylation.

The associations of four single nucleotide polymorphisms (p.Arg194Trp, p.Arg280His, p.Pro206Pro, and p.Arg399Gln) in X-ray repair cross-complementing group 1 with urinary arsenic metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated in a Vietnamese population (n = 100). Individuals with genotype AA in p.Pro206Pro showed significantly higher urinary monomethylarsonic acid (MMA(V)) and lower dimethylarsinic acid (DMA(V))/MMA(V) ratio than genotype AG. As for p.Arg399Gln, both Arg/Arg homozygous subjects and Arg/Gln heterozygous individuals showed a significantly higher urinary inorganic As percentage and lower 8-OHdG concentrations than Gln/Gln homozygous. Our results suggested that Arg399Gln is a functional SNP that may be related to DNA repair activity.

In Vitro and in Silico Analyses for Predicting Hepatic Cytochrome P450-Dependent Metabolic Potencies of Polychlorinated Biphenyls in the Baikal Seal.

The aim of this study was to understand the cytochrome P450 (CYP)-dependent metabolic pathway and potency of polychlorinated biphenyls (PCBs) in the Baikal seal (Pusa sibirica). In vitro metabolism of 62 PCB congener mixtures was investigated by using liver microsomes of this species. A decreased ratio of over 20% was observed for CB3, CB4, CB8, CB15, CB19, CB22, CB37, CB54, CB77, and CB105, suggesting the preferential metabolism of low-chlorinated PCBs by CYPs. The highly activated metabolic pathways in Baikal seals that were predicted from the decreased PCBs and detected hydroxylated PCBs (OH-PCBs) were CB22 to 4'OH-CB20 and CB77 to 4'OH-CB79. The total amount of OH-PCBs detected as identified and unidentified congeners accounted for only a 3.8 ± 1.7 mol % of loaded PCBs, indicating many unknown PCB metabolic pathways. To explore factors involved in CYP-dependent PCB metabolism, we examined the relationships among the structural and physicochemical properties of PCBs, the in silico PCB-CYP docking parameters, and the in vitro PCB decreased ratios by principal component analysis. Statistical analysis showed that the decreased PCB ratio was at least partly accounted for by the substituted chlorine number of PCBs and the distance from the Cl-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and 2B.

Uptake and Tissue Distribution of Pharmaceuticals and Personal Care Products in Wild Fish from Treated-Wastewater-Impacted Streams.

A fish plasma model (FPM) has been proposed as a screening technique to prioritize potential hazardous pharmaceuticals to wild fish. However, this approach does not account for inter- or intraspecies variability of pharmacokinetic and pharmacodynamic parameters. The present study elucidated the uptake potency (from ambient water), tissue distribution, and biological risk of 20 pharmaceutical and personal care product (PPCP) residues in wild cyprinoid fish inhabiting treated-wastewater-impacted streams. In order to clarify the uncertainty of the FPM for PPCPs, we compared the plasma bioaccumulation factor in the field (BAFplasma = measured fish plasma/ambient water concentration ratio) with the predicted plasma bioconcentration factor (BCFplasma = fish plasma predicted by use of theoretical partition coefficients/ambient water concentration ratio) in the actual environment. As a result, the measured maximum BAFplasma of inflammatory agents was up to 17 times higher than theoretical BCFplasma values, leading to possible underestimation of toxicological risk on wild fish. When the tissue-blood partition coefficients (tissue/blood concentration ratios) of PPCPs were estimated, higher transportability into tissues, especially the brain, was found for psychotropic agents, but brain/plasma ratios widely varied among individual fish (up to 28-fold). In the present study, we provide a valuable data set on the intraspecies variability of PPCP pharmacokinetics, and our results emphasize the importance of determining PPCP concentrations in possible target organs as well as in the blood to assess the risk of PPCPs on wild fish.

Toxic Identification and Evaluation of Androgen Receptor Antagonistic Activities in Acid-Treated Liver Extracts of High-Trophic Level Wild Animals from Japan.

Sulfuric acid-treated liver extracts of representative high-trophic level Japanese animals were analyzed by toxic identification and evaluation (TIE) with chemically activated luciferase expression (CALUX) and chemical analysis to elucidate androgen receptor (AR) antagonistic activities and potential contributions of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). The activities were detected in striped dolphins (n = 5), Stejneger's beaked whales (n = 6), golden eagle (n = 1), and Steller's sea eagle (n = 1) with CALUX-flutamide equivalents (FluEQs) as follow: 38 (20-52), 47 (21-96), 5.0, and 80 µg FluEQ/g-lipid, respectively. The AR antagonism was detected in limited number of specimens at lower levels for finless porpoise, raccoon dog, and common cormorant. Theoretical activities (Theo-FluEQs) were calculated using the concentration of OCPs and PCBs and their IC25-based relative potency (REP) values. These total contribution to CALUX-FluEQ was 126%, 84%, 53%, 55%, and 44% for striped dolphin, Steller's sea eagle, Stejneger's beaked whale, finless porpoise, and golden eagle, respectively, and the main contributor was p,p'-DDE. However, most of the activities for raccoon dog (7.6%) and common cormorant (17%) could not be explained by OCPs and PCBs. This suggests other unknown compounds could function as AR antagonists in these terrestrial species.

Organohalogens and their hydroxylated metabolites in the blood of pigs from an open waste dumping site in south India: association with hepatic cytochrome P450.

The concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and their hydroxylated metabolites (OH-PCBs and OH-PBDEs) were measured in the blood of Eurasian wild pigs (Sus scrofa) from a municipal waste open dumping site (DS) and a reference site (RS) in South India. We showed that contamination with OH-PCBs was higher in female pigs from the DS than in all other adult pigs. The highest OH-PCB concentrations were found in piglets from the DS. Moreover, the hepatic expression levels of CYP1A and CYP2B were higher in piglets than in their dam, implying metabolism of PCBs by cytochrome P450 (CYP) enzymes. The OH-PCB congener profiles differed according to sex and collection sites, possibly because of variations in the expression levels of phase I and phase II enzymes among individual pigs, differences in the exposure sources, and maternal transfer of parent PCBs. The hepatic CYP1A expression levels were positively correlated with the blood concentrations of 4OH-CB107, 4OH-CB162, and 4OH-CB187, implying CYP1A-dependent formation of these OH-PCBs in the pig liver. We found no significant correlations between the blood concentrations of OH-PCBs and thyroid hormones (THs); however, the thyroxin (T4) levels were lower in pigs from the DS than in pigs from the RS. Our limited dataset suggest that induced CYP enzymes accelerate the metabolism of xenobiotics and endogenous molecules in pigs. Thus, besides parental compounds, the risk of hydroxylated metabolites entering wildlife and humans living in and around municipal open waste dumping sites should be considered.

Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam: Association with thyroid hormone levels.

This study demonstrated the contamination levels of polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs), methoxylated PBDEs (MeO-PBDEs), hydroxylated PBDEs (OH-PBDEs), and bromophenols (BPhs), and their relationships with thyroid hormones (THs), in the serum of human donors from an e-waste recycling site and a rural site in Hung Yen province, Vietnam. Occupationally related exposure was indicated by significantly higher residue levels of PCBs, OH-PCBs, PBDEs, and BPhs in the serum of donors from the e-waste recycling site (median: 420, 160, 290, and 300pgg(-1) wet wt, respectively) than those in the serum of donors from the rural site (median: 290, 82, 230, and 200pgg(-)(1) wet wt, respectively). On the other hand, levels of OH-/MeO-PBDEs were significantly higher in serum of donors from the reference site (median: 160 and 20pgg(-1) wet wt, respectively) than in those from the e-waste recycling site (median: 43 and 0.52pgg(-1) wet wt, respectively). In addition, we implemented stepwise generalized linear models to assess the association between the levels of TH and PCBs, PBDEs, and their related compounds. In females, we found positive associations of PCBs and OH-PCB concentrations with total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine, and a negative association with thyroid-stimulating hormone concentrations.

Toxicological assessment of polychlorinated biphenyls and their metabolites in the liver of Baikal seal (Pusa sibirica).

We have previously reported that high accumulation of dioxins and related compounds induced cytochrome P450 (CYP 1s) isozymes in the liver of wild Baikal seals, implying the enhanced hydroxylation of polychlorinated biphenyls (PCBs). The present study attempted to elucidate the residue concentrations and patterns of PCBs and hydroxylated PCBs (OH-PCBs) in the livers of Baikal seals. The hepatic residue concentrations were used to assess the potential effects of PCBs and OH-PCBs in combination with the analyses of serum thyroid hormones, hepatic mRNA levels, and biochemical markers. The hepatic expression levels of CYP1 genes were positively correlated with the concentration of each OH-PCB congener. This suggests chronic induction of these CYP1 isozymes by exposure to PCBs and hydroxylation of PCBs induced by CYP 1s. Hepatic mRNA expression monitoring using a custom microarray showed that chronic exposure to PCBs and their metabolites alters the gene expression levels related to oxidative stress, iron ion homeostasis, and inflammatory responses. In addition, the concentrations of OH-PCBs were negatively correlated with L-thyroxine (T4) levels and the ratios of 3,3',5-triiodo-L-thyronine (T3)/reverse 3,3',5'-triiodo-L-thyroninee (rT3). These observations imply that Baikal seals contaminated with high levels of OH-PCBs may undergo the disruption of mechanisms related to the formation (or metabolism) of T3 and T4 in the liver.

A microcosm approach to evaluate the degradation of tributyltin (TBT) by Aeromonas molluscorum Av27 in estuarine sediments.

Tributyltin (TBT) is a biocide extremely toxic to a wide range of organisms, which has been used for decades in antifouling paints. Despite its global ban in 2008, TBT is still a problem of great concern due to the high levels trapped in sediments. Aeromonas molluscorum Av27 is a TBT degrading bacterium that was isolated from an estuarine system. We investigated the ability and the role of this bacterium on TBT degradation in this estuarine system, using a microcosm approach in order to mimic environmental conditions. The experiment was established and followed for 150 days. Simultaneously, changes in the indigenous bacterial community structure were also investigated. The results revealed a maximum TBT degradation rate of 28% accompanied by the detection of the degradation products over time. Additionally, it was observed that TBT degradation was significantly enhanced by the presence of Av27. In addition a significantly higher TBT degradation occurred when the concentration of Av27 was higher. TBT degradation affected the bacterial community composition as revealed by the changes in the prevalence of Proteobacteria subdivisions, namely the increase of Deltaproteobacteria and the onset of Epsilonproteobacteria. However, the addition of Av27 strain did not affect the dominant phylotypes. Total bacterial number, bacterial biomass productivity, 16S rRNA gene and denaturing gradient gel electrophoresis (DGGE) analyses also indicated alterations on the bacterial community structure over time, with bacteria non-tolerant to pollutants increasing their representativeness, as, for instance, the increase of the number of Alphaproteobacteria clones from 6% in the beginning to 12% at the end of the experiment. The work herein presented confirms the potential of Av27 strain to be used in the decontamination of TBT-polluted environments.

Dioxin-related compounds in breast milk of women from Vietnamese e-waste recycling sites: levels, toxic equivalents and relevance of non-dietary exposure.

Although informal e-waste recycling sites (EWRSs) are hotspots of both polychlorinated and polybrominated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs and PBDD/Fs), human exposure to the latter has not been studied in details. This study investigated the accumulation levels and profiles of dioxin-related compounds (DRCs) in breast milk samples from women living in two Vietnamese EWRSs and estimated the intake contribution from e-waste-related exposure. Screening results using Dioxin-Responsive Chemically Activated LUciferase gene eXpression assay (DR-CALUX) showed higher dioxin-like (DL) activities in samples from the EWRS Bui Dau than in those from the EWRS Trang Minh and a reference site (2.3-10 vs 1.7-4.8 and 0.60-5.7 pg CALUX-TEQ/g lipid, n=10, 6 and 9, respectively). Chemical analysis results of selected samples show that the WHO-TEQ levels of PCDD/Fs, DL-PCBs and PBDD/Fs in EWRS samples were not significantly higher than in those from the reference site (0.22-7.4 vs 1.1-3.0 pg/g lipid) and within the Vietnamese background range, but women involved in recycling accumulated higher concentrations of PCDFs (13-15 vs 2.3-8.8 pg/g lipid) and PBDFs (1.1-1.5 vs <1.1 pg/g lipid). By comparing the DRC profile in milk of these women with the reported profile in house dust from the same site, dust ingestion was estimated to contribute most of the intake for tetraBDF, 37 per cent to 55 per cent for penta-octaCDFs, but less than twenty per cent for PCDDs and DL-PCBs, and 26 per cent for total WHO-TEQs. The DL activities in some EWRS milk samples were not fully explained by chemical data, suggesting contribution from unidentified compounds. The estimated WHO-TEQ intake doses for breastfed infants (1.3-33 pg/kg/d) mostly exceeded the tolerable value, especially for those living in the EWRSs; and unidentified DRCs might increase further the dioxin-related health risk.

Effects of persistent organochlorine exposure on the liver transcriptome of the common minke whale (Balaenoptera acutorostrata) from the North Pacific.

Hepatic concentrations of persistent organochlorines (OCs) were determined in the common minke whale (Balaenoptera acutorostrata) from the North Pacific. To investigate the effects of OCs on the transcriptome in the minke whale, the present study constructed a hepatic oligo array of this species where 985 unique oligonucleotides were spotted and further analyzed the relationship between the OC levels and gene expression profiles of liver tissues. The stepwise multiple linear regression analysis identified 32 genes that correlated with hepatic OC levels. The mRNA expression levels of seven cytochrome P450 (CYP) genes, CYP1A1, 1A2, 2C78, 2E1, 3A72, 4A35, and 4V6 showed no clear correlations with the concentration of each OC, suggesting that the accumulated OCs in the liver did not reach levels that could alter CYP expression. Among the genes screened by the custom oligo array analysis, hepatic mRNA expression levels of 16 genes were further measured using quantitative real-time reverse transcription polymerase chain reaction. The mRNA levels of vitamin D-binding protein (DBP) were negatively correlated with non-ortho coplanar polychlorinated biphenyl (PCB) levels. Androgen receptor-associated coregulator 70 (ARA70) expression levels showed a significant positive correlation with concentrations of non-ortho coplanar PCB169. These correlations suggest that coplanar PCB-reduced DBP expression could suppress vitamin D receptor-mediated signaling cascades in peripheral tissues. Alternatively, the suppression of vitamin D receptor signaling cascade could be enhanced through competition with the androgen receptor signaling pathway for ARA70. In addition, a negative correlation between kynureninase and PCB169 levels was also observed, which suggest an enhanced accumulation of an endogenous aryl hydrocarbon receptor agonist, kynurenine in the minke whale population. Further studies are necessary to translate the changes in the transcriptome to toxicological outcomes including the disruption of the nervous and immune systems.