Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.tox.2023.153687

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ecoenv.2023.115495

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

In Asian developing countries, undeveloped and ineffective sewer systems are causing surface water pollution by a lot of contaminants, especially pharmaceuticals and personal care products (PPCPs). Therefore, the risks for freshwater fauna need to be assessed. The present study aimed at: i) elucidating the contamination status; ii) evaluating the bioaccumulation; and iii) assessing the potential risks of PPCP residues in surface water and freshwater fish from three Asian countries. We measured 43 PPCPs in the plasma of several fish species as well as ambient water samples collected from India (Chennai and Bengaluru), Indonesia (Jakarta and Tangerang), and Vietnam (Hanoi and Hoa Binh). In addition, the validity of the existing fish blood–water partitioning model based solely on the lipophilicity of chemicals is assessed for ionizable and readily metabolizable PPCPs. When comparing bioaccumulation factors calculated from the PPCP concentrations measured in the fish and water (BAFmeasured) with bioconcentration factors predicted from their pH-dependent octanol–water partition coefficient (BCFpredicted), close values (within an order of magnitude) were observed for 58–91 % of the detected compounds. Nevertheless, up to 110 times higher plasma BAFmeasured than the BCFpredicted were found for the antihistamine chlorpheniramine in tilapia but not in other fish species. The plasma BAFmeasured values of the compound were significantly different in the three fish species (tilapia > carp > catfish), possibly due to species-specific differences in toxicokinetics (e.g., plasma protein binding and hepatic metabolism). Results of potential risk evaluation based on the PPCP concentrations measured in the fish plasma suggested that chlorpheniramine, triclosan, haloperidol, triclocarban, diclofenac, and diphenhydramine can pose potential adverse effects on wild fish. Results of potential risk evaluation based on the PPCP concentrations measured in the surface water indicated high ecological risks of carbamazepine, sulfamethoxazole, erythromycin, and triclosan on Asian freshwater ecosystems.

DOI： 10.1016/j.scitotenv.2022.161258

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOP Publishing  

Abstract

Contamination by emerging contaminants of pharmaceutical and personal care products (PPCPs) has been a matter of global concern due to increasing their occurrence in the environment and their potential toxic effect. Despite the increasing number of publications on PPCPs in aquatic environments worldwide, only very few data are available in Indonesia. This study aims to determine PPCPs in the surface water of Jakarta Bay to understand their occurrence and distribution. Surface water was collected from 17 stations in September 2018. Samples were analyzed for 74 compounds of PPCPs using Ultra-fast Liquid Chromatography coupled with mass spectrometry. In general, among PPCPs analyzed, 20 compounds occur in seawater from Jakarta Bay, of which 15 PPCPs were detected in 50% of the sampling stations. Among PPCPs detected, N,N-diethyl-3-toluamide (DEET), Ibuprofen, O-desmethyl tramadol, Mefenamic acid, Sulfamethoxazole and Tramadol were the predominant with mean and range concentrations of 51(nd-170), 6.9(nd-22), 6.5(nd-31), 4.8(nd-13), 2.2(nd-6.1), and 131.9(nd-4.8) ng/l, respectively. Whereas the other PPCPs were one or more orders of magnitude lower. Generally, concentrations of PPCPs were higher in the inner bay than outer bays. Another study from freshwater rivers which flow to Jakarta Bay showed a high concentration of DEET indicating that the environment was an essential source of PPCPs.

DOI： 10.1088/1755-1315/1137/1/012050

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Other Link： https://iopscience.iop.org/article/10.1088/1755-1315/1137/1/012050/pdf

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Wild carnivorans are one of the most important species due to their high positions in the food chain. They are also highly affected by numerous environmental contaminants through bioaccumulation and biomagnification. Xenobiotic metabolism is a significant chemical defense system from xenobiotics because it degrades the activity of a wide range of chemicals, generally into less active forms, resulting in their deactivation. Sulfotransferases (SULTs) are one of the most important xenobiotic metabolic enzymes, which catalyze the sulfonation of a variety of endogenous and exogenous chemicals, such as hormones, neurotransmitters, and a wide range of xenobiotic compounds. Although SULTs are of such high importance, little research has focused on these enzymes in wild carnivorans. In this study, we clarified the genetic properties of SULTs in a wide range of mammals, focusing on carnivorans, using in silico genetic analyses. We found genetic deficiencies of SULT1E1 and SULT1D1 isoforms in all pinnipeds analyzed and nonsense mutations in SULT1Cs in several carnivorans including pinnipeds. We further investigated the enzymatic activity of SULT1E1 in vitro using liver cytosols from pinnipeds. Using a SULT1E1 probe substrate, we found highly limited estradiol sulfonation in pinnipeds, whereas other mammals had relatively high sulfation. These results suggest that pinnipeds have severely or completely absent SULT1E1 activity, which importantly catalyzes the metabolism of estrogens, drugs, and environmental toxins. This further implies a high susceptibility to a wide range of xenobiotics in these carnivorans, which are constantly exposed to environmental chemicals throughout their lifetime.

DOI： 10.1016/j.cbpc.2022.109476

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Language：English   Publishing type：Research paper (scientific journal)  

As an animal familiar to humans, cats are considered to be sensitive to chemicals; cats may be exposed to polychlorinated biphenyls (PCBs) and decabromodiphenyl ether (BDE-209) from indoor dust, household products, and common pet food, leading to adverse endocrine effects, such as thyroid hormone dysfunction. To elucidate the general biological effects resulting from exposure of cats to PCBs and PBDEs, cats were treated with a single i.p. dose of a principal mixture of 12 PCBs and observed for a short-term period. Results revealed that the testis weight, serum albumin, and total protein of the treated group decrease statistically in comparison with those in the control group. The negative correlations suggested that the decrease in the total protein and albumin levels may be disturbed by 4'OH-CB18, 3'OH-CB28 and 3OH-CB101. Meanwhile, the serum albumin level and relative brain weight decreased significantly for cats subjected to 1-year continuous oral administration of BDE-209 in comparison to those of control cats. In addition, the subcutaneous fat as well as serum high-density lipoprotein (HDL) and triglycerides (TG) levels increased in cats treated with BDE-209 and down-regulation of stearoyl-CoA desaturase mRNA expression in the liver occurred. These results suggested that chronic BDE-209 treatment may restrain lipolysis in the liver, which is associated with lipogenesis in the subcutaneous fat. Evidence of liver and kidney cell damage was not observed as there was no significant difference in the liver enzymes, blood urea nitrogen and creatinine levels between the two groups of both experiments. To the best of our knowledge, this is the first study that provides information on the biochemical effects of organohalogen compounds in cats. Further investigations on risk assessment and other potential health effects of PCBs and PBDEs on the reproductive system, brain, and lipid metabolism in cats are required.

DOI： 10.1371/journal.pone.0277689

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

In this study, we analyzed serum samples of pet cats from Thailand and estimated the contribution to organohalogen compounds (OHCs) exposure through cat food and house dust intake. BDE-209 was predominant in cat sera and accounted for 76% of all polybrominated diphenyl ethers (PBDEs). Decabromodiphenyl ether (BDE-209) is a major contaminant in dry cat food and house dust, which has been estimated to be a source of exposure for Thai pet cats. BDE-209 is a major contaminant of OHCs in dry cat food and house dust, which was estimated to be a source of exposure for Thai pet cats. On the other hand, the level of contamination by PCBs was lower than in other countries. Analysis of pet foods suggested that BDE-209 in pet cat serum was attributable to the consumption of dry cat food. On the other hand, house dust also contained high concentrations of BDE-209. Thus, high levels of BDE-209 in pet cat sera can be attributed to the consumption of dry cat food and house dust. These results suggest that pet cats are routinely exposed to non-negligible levels of OHCs.

DOI： 10.3390/ani12243520

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Language：English   Publishing type：Research paper (scientific journal)  

Monoamine neurotransmitters (MAs), including dopamine (DA) and serotonin (5-HT), regulate brain functions such as behavior, memory, and learning. Neonicotinoids are pesticides that are being used more frequently. Neonicotinoid exposure has been observed to produce neurological symptoms, such as altered spontaneous movements and anxiety-like behaviors, which are suspected to be caused by altered MA levels. However, current neurotoxicity tests are not sufficiently sensitive enough to make these determinations. In this study, we performed some behavior tests, and derivatization reagents to improve the ionization efficiency, which was applied to liquid chromatography mass spectrometry (LC-MS/MS) to reveal the effect of neonicotinoid administration on MAs in the brain. We orally administered the neonicotinoid imidacloprid (0, 10, and 50 mg/kg body weight) to C57BL/6NCrSlc mice. In the behavior tests, a decrease in activity was observed. The LC-MS/MS quantification of MAs in various brain regions showed a decrease in some MA levels in the olfactory bulb and the striatum. These results showed, for the first time, that even a low dose of imidacloprid could alter MA levels in various parts of the brain.

DOI： 10.3390/toxics10110696

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Companion animals are in close contact with the human surroundings, and there is growing concern about the effects of harmful substances on the health of pet cats. In this study, we investigated the potential health effects of organohalogen compounds (OHCs) on thyroid hormone (TH) homeostasis and metabolomics in Japanese pet cats. There was a significant negative correlation between concentrations of several contaminants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hydroxylated PCBs (OH-PCBs), hydroxylated PBDEs (OH-PBDEs), and THs in cat serum samples. These results suggested that exposure to OHCs causes a decrease in serum TH levels in pet cats. In this metabolomics study, each exposure level of parent compounds (PCBs and PBDEs) and their hydroxylated compounds (OH-PCBs and OH-PBDEs) were associated with their own unique primary metabolic pathways, suggesting that parent and phenolic compounds exhibit different mechanisms of action and biological effects. PCBs were associated with many metabolic pathways, including glutathione and purine metabolism, and the effects were replicated in in-vivo cat PCB administration studies. These results demonstrated that OHC exposure causes chronic oxidative stress in pet cats. PBDEs were positively associated with alanine, aspartate, and glutamate metabolism. Due to the chronic exposure of cats to mixtures of these contaminants, the combination of their respective metabolic pathways may have a synergistic effect.

DOI： 10.1016/j.scitotenv.2022.156490

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Authorship：Lead author,　Corresponding author   Language：Japanese  

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.chroma.2021.462686

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

The presence of pharmaceutically active compounds (PACs) in the environment and their associated hazards is a major global health concern; however, data on these compounds are scarce in developing nations. In the present study, the existence of 39 non-antimicrobial PACs and six of their metabolites in wastewater from hospitals and adjacent surface waters in Sri Lanka was investigated from 2016-2018. The highest amount of the measured chemicals, including the highest concentrations of atorvastatin (14,620 ng/L) and two metabolites, mefenamic acid (12,120 ng/L) and o-desmethyl tramadol (8,700 ng/L), were detected in wastewater from the largest facility. Mefenamic acid, gemfibrozil, losartan, cetirizine, carbamazepine, and phenytoin were detected in all the samples. The removal rates in wastewater treatment were 100% for zolpidem, norsertaline, quetiapine, chlorpromazine, and alprazolam. There was substantial variation in removal rates of PACs among facilities, and the overall data suggest that treatment processes in facilities were ineffective and that some PAC concentrations in the effluents were increased. The estimated risk quotients revealed that 14 PACs detected in water samples could pose low to high ecological risk to various aquatic organisms. Compounds such as ibuprofen, tramadol, and chlorpromazine detected in untreated and treated wastewater at these facilities pose a high risk to several aquatic organisms. This study provides novel monitoring data for non-antimicrobial PAC abundance and the associated potential ecological risk related to hospitals and urban surface waters in Sri Lanka and further offers invaluable information on pre-COVID-19 era PAC distribution in the country. This article is protected by copyright. All rights reserved.

DOI： 10.1002/etc.5212

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.chemosphere.2021.130591

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.pestbp.2021.104847

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Previous studies have suggested that unidentified compounds constitute a large proportion of extractable organochlorine (EOCl) and extractable organobromine (EOBr) in the crude extracts without fractionation; however, the proportion of unidentified EOX (X = chlorine, bromine) associated with high-/low-molecular-weight compounds is still unknown. In this study, we applied gel permeation chromatography to fractionate extracts from archived liver samples of high-trophic marine and terrestrial mammals (striped dolphins, cats, and raccoon dogs), for which concentrations of legacy organohalogen contaminants (polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers [PBDEs]) had been previously reported. EOX in high- (>1000 g/mol) and low- (≤1000 g/mol) molecular-weight fractions (EOX-H and EOX-L) were determined by neutron activation analysis. Comparison of EOCl and EOBr enabled the characterization among species. Despite small differences in the concentrations and molecular-weight profiles of EOCl among species, the contribution of chlorine in identified compounds to EOCl-L varied from 1.5% (cats) to 79% (striped dolphins). Considerable species-specific variations were observed in the concentrations of EOBr: striped dolphins exhibited significantly greater concentrations of both EOBr-H and EOBr-L than cats and/or raccoon dogs. Moreover, the contribution of bromine in PBDEs to EOBr-L was >50% in two cats, while it was <6% in other specimens. This is the first report on EOBr mass balance in cetaceans and on EOX mass balance in terrestrial mammals living close to humans. These results suggest the need for analysis of unidentified chlorinated compounds in terrestrial mammals and unidentified brominated compounds in marine mammals.

DOI： 10.1016/j.scitotenv.2020.143843

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Language：English   Publishing type：Research paper (scientific journal)  

Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. However, CYP activities and metabolite compositions of neonicotinoid metabolites are unknown in most domesticated pet species. Our objectives were to reveal the differences in metabolites of neonicotinoids (imidacloprid, clothianidin, and acetamiprid) and CYP activities among common pet species (cats and dogs), humans, and rats. The results indicated that the CYP-mediated neonicotinoid metabolism was different depending on species and each neonicotinoid. Among these four species, the kinetics of imidacloprid metabolism indicated that rats have the highest rate of oxidation of imidacloprid to 4OH-imidacloprid, while the greatest enzyme kinetics of imidacloprid metabolism to 5OH-imidacloprid were found in rats and humans. Clothianidin was rapidly metabolized to 1-methyl-3-nitroguanidine and dm-clothianidin in rats, but cats and humans showed the lowest formation of dm-clothianidin. CYP activities in metabolism of acetamiprid to dm-acetamiprid and N-acetyl-acetamiprid were determined to be significantly higher in humans compared to other species. However, further studies should be targeted at identifying the differences in hepatic metabolism of neonicotinoids in these species using recombinant CYP enzymes.

DOI： 10.1016/j.cbpc.2020.108898

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J-GLOBAL

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.chroma.2020.461586

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1021/acs.est.0c01805

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Language：English   Publishing type：Research paper (scientific journal)  

The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.

DOI： 10.1292/jvms.20-0140

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Language：English   Publishing type：Research paper (scientific journal)  

Cats have been known to be extremely sensitive to chemical exposures. To understand these model species' sensitivity to chemicals and their toxicities, the expression profiles of xenobiotic-metabolizing enzymes should be studied. Unfortunately, the characterization of cytochrome P450 (CYP), the dominant enzyme in phase I metabolism, in cats has not extensively been studied. Polychlorinated biphenyls (PCBs) are known as CYP inducers in animals, but the information regarding the PCB-induced CYP expression in cats is limited. Therefore, in the present study, we aimed to elucidate the mRNA expression of the CYP1-CYP3 families in the cat tissues and to investigate the CYP mRNA expression related to PCB exposure. In cats, the greatest abundance of CYP1-CYP3 (CYP1A2, CYP2A13, CYP2C41, CYP2D6, CYP2E1, CYP2E2, CYP2F2, CYP2F5, CYP2J2, CYP2U1, and CYP3A132) was expressed in the liver, but some extrahepatic isozymes were found in the kidney (CYP1A1), heart (CYP1B1), lung (CYP2B11 and CYP2S1) and small intestine (CYP3A131). In cats, CYP1A1, CYP1A2 and CYP1B1 were significantly upregulated in the liver as well as in several tissues exposed to PCBs, indicating that these CYPs were distinctly induced by PCBs. The strong correlations between 3,3',4,4'-tetrachlorobiphenyl (CB77) and CYP1A1 and CYP1B1 mRNA expressions were noted, demonstrating that CB77 could be a potent CYP1 inducer. In addition, these CYP isoforms could play an essential role in the PCBs biotransformation, particularly 3-4 Cl-PCBs, because a high hydroxylated metabolite level of 3-4 Cl-OH-PCBs was observed in the liver.

DOI： 10.1016/j.cbpc.2019.108613

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© 2019 Pharmaceuticals and personal care products (PPCPs) are known as an emerging class of water contaminants due to their potential adverse effects on aquatic ecosystems. In this study, we conducted the first nationwide survey to understand the distribution and environmental risk of 72 PPCPs in surface waterways of Sri Lanka. Forty-one out of 72 targeted compounds were detected with total concentrations ranging between 5.49 and 993 ng/L in surface waterways in Sri Lanka. The highest level of PPCP contamination was detected in an ornamental fish farm. Sulfamethoxazole was found with the highest concentration (934 ng/L) followed by N,N-diethyl-meta-toluamide (202 ng/L) and clarithromycin (119 ng/L). Diclofenac, mefenamic acid, ibuprofen, trimethoprim, and erythromycin were detected ubiquitously throughout the country. Our data revealed that hospital and domestic wastewater, and aquaculture activities potentially contribute to the presence of PPCPs in Sri Lankan waterways. The calculated risk quotients indicated that several locations face medium to high ecological risk to aquatic organisms from ibuprofen, sulfamethoxazole, diclofenac, mefenamic acid, tramadol, clarithromycin, ciprofloxacin, triclocarban, and triclosan. The aforementioned compounds could affect aquatic organisms from different trophic levels like algae, crustacean and fish, and also influence the emergence of antibiotic resistant bacteria. These findings emphasize that a wide variety of pharmaceuticals have become pervasive environmental contaminants in the country. This data will serve to expand the inventory of global PPCP pollution. Further monitoring of PPCPs is needed in Sri Lanka in order to identify PPCP point sources and to implement strategies for contaminant reduction in wastewater to protect the aquatic ecosystem, wildlife, and human health.

DOI： 10.1016/j.scitotenv.2019.07.042

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism.

DOI： 10.1016/j.scitotenv.2019.06.300

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1016/j.taap.2019.114620

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DOI： 10.1016/j.scitotenv.2019.02.090

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Language：English   Publishing type：Part of collection (book)   Publisher：Springer International Publishing  

There are growing concerns about health risks in pet animals due to the exposure to brominated compounds. This chapter describes the available information on tissue-specific accumulation and biotransformation of PBDEs and their hydroxylated and methoxylated derivatives (OH-PBDEs and MeO-PBDEs) in pet dogs and cats. Cats tend to exhibit higher tissueand blood concentrations of PBDEs. Furthermore, brominated compounds are also found at relatively high concentrations in cat brains, suggesting that they can cross through the blood–brain barrier. Thus, cats might be at a high risk from PBDEs and their derivatives. In dogs, BDE47 is the dominant congener in the bile, which suggests a species-specific excretory capacity of the liver. Regarding PBDEs metabolites, 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. The profiles and tissue distribution of PBDEs and metabolites are described for both species, and possible explanations for the differencesobserved between these pets are put forward.

DOI： 10.1007/978-3-030-30734-9_6

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DOI： 10.1016/j.envpol.2018.06.071

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Language：English   Publishing type：Research paper (scientific journal)  

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have been detected in tissues of both wild animals and humans. Several previous studies have suggested adverse effects of OH-PCBs on the endocrine and nervous systems in mammals. However, there have been no studies on transcriptome analysis of the effects of OH-PCBs, and thus, the whole picture and mechanisms underlying the adverse effects induced by OH-PCBs are still poorly understood. We therefore investigated the mRNA expression profile in the liver of adult male Wistar rats treated with 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to explore the genes responsive to OH-PCBs and to understand the potential effects of the chemical. Next-generation RNA sequencing analysis revealed changes in the expression of genes involved in the circadian rhythm and fatty acid metabolism, such as nuclear receptor subfamily 1, group D, member 1, aryl hydrocarbon receptor nuclear translocator-like protein 1, cryptochrome circadian clock 1, and enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase, in 4-OH-CB107-treated rats. In addition, biochemical analysis of the plasma revealed a dose-dependent increase in the leucine aminopeptidase, indicating the onset of liver damage. These results suggest that OH-PCB exposure may induce liver injury as well as disrupt the circadian rhythm and peroxisome proliferator-activated receptor-related fatty acid metabolism.

DOI： 10.1093/toxsci/kfy123

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Language：Japanese  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

Thyroid hormones (THs), which mainly consist of 3, 3′ 5-triiodo-L-thyronine (T3) and L-thyroxine (T4), play a critical role in regulating biological processes such as growth and metabolism in various animal species. Thus, accurate measurement of T3 and T4, especially physiologically active free (protein-unbound) forms, in serum/plasma is needed for the evaluation of TH homeostasis. However, such high-precision determination of free THs is lacking for non-human species. The present study aimed to develop a highly sensitive and reliable liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for the determination of six free THs in serum/plasma, which is applicable to not only humans but also non-human species. Two different physical separation steps, ultrafiltration (UF) and equilibrium dialysis (ED), were examined to obtain the free TH fraction. Several experimental conditions were carefully optimized and validated for UF or ED using the commercially available bovine serum. As a result, UF at 1100 × g and 37 °C for 30 min with a 30 kDa ultrafiltration device (Centrifree YM-30, Millipore) yielded excellent precision (CV: &lt
10%). The optimized ED step also yielded high precision (CV: &lt
10%) and the measurement values were approximately equal to those of UF, but at least 16 h were required to reach equilibrium. Thus, UF combined with LC–MS/MS was finally chosen, in terms of the time needed for the measurement. Acceptable accuracy (recovery: 70%–110%) and intra- and inter-day precision (CV: &lt
10% and &lt
12%, respectively) were obtained, when triplicate analyses in three different days were conducted using the bovine serum. The developed analytical method was successfully applied to the determination of free THs in serum/plasma samples of humans, cats, and dogs. Furthermore, comparison with free T4 concentrations measured by a common immunoassay method evidently indicated that the ultrafiltration-LC–MS/MS method developed in this study can increase the specificity and accuracy of TH measurement.

DOI： 10.1016/j.chroma.2018.01.044

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Lead (Pb) poisoning is widespread among raptors and water birds. In Japan, fragments of Pb ammunition are still found in endangered eagles although more than 10 years have passed since legislation regarding use of Pb ammunition was introduced. This study was performed to investigate Pb exposure in raptors from various locations in Japan. We measured hepatic and renal Pb concentrations and hepatic Pb isotope ratios of Steller's sea eagles (Haliaeetus pelagicus), white-tailed sea eagles (Haliaeetus albicilla), golden eagles (Aquila chrysaetos), and 13 other species (total 177 individuals) that were found dead, as well as blood samples from three eagles found in a weakened state during 1993-2015 from Hokkaido (northern part), Honshu (the main island), and Shikoku (a southern island) of japan. In the present study in Hokkaido, one quarter of the sea eagles showed a high Pb concentration, suggesting exposure to abnormally high Pb levels and Pb poisoning. Pb isotope ratios indicated that endangered Steller's sea eagle and white-tailed sea eagle were poisoned by Pb ammunition that was used illegally in Hokkaido. In other areas of Japan, both surveillance and regulations were less extensive than in Hokkaido, but Pb poisoning in raptors was also noted. Therefore, Pb poisoning is still a serious problem in raptors in various areas of Japan due to accidental ingestion of materials containing Pb, especially Pb ammunition. (C) 2017 Published by Elsevier Ltd.

DOI： 10.1016/j.chemosphere.2017.07.143

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

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.

DOI： 10.1021/acs.est.7b03441

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

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 (&gt;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 &gt;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.

DOI： 10.1021/acs.est.7b01009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Detailed composition of chlorinated and brominated polycyclic aromatic hydrocarbons (Cl-PAHs and Br-PAHs) generated during informal recycling of e-waste and their toxic relevance are still poorly understood. This study investigated the occurrence of Cl-PAHs and Br-PAHs in surface soil samples from the Agbogbloshie e-waste recycling site (Accra, Ghana) using quantitative gas chromatography-mass spectrometry (GC-MS) and comprehensive two-dimensional GC-time-of-flight mass spectrometry (GC x GC-ToFMS) profiling. The results of GC-MS analysis showed elevated concentrations in open e-waste burning areas (160-220 and 19-46 ng/g dry weight for Cl- and Br-PAHs, respectively) with substantial contribution from unidentified compounds (respectively, more than 36 and 70%, based on the total areas of potential peaks). Cl- and Br-PAHs from e-waste burning had a distinctive composition dominated by ring-ring compounds. Several homologue groups not monitored with GC-MS were found using GC x GC-ToFMS: PAHs with up to 5 Cl or 3Br, mixed halogenated PAHs and chlorinated methylPAHs. The dioxin-like toxic equivalents of the identified Cl-/Br-PAHs in soils, estimated from their in vitro AhR agonist potencies relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin, were much lower than the range reported for chlorinated and brominated dioxins. However, the toxicity of the unidentified halogenated PAHs remained unclear.

DOI： 10.1007/s10163-016-0568-y

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Other Link： http://orcid.org/0000-0002-8012-3806

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

This study investigated the accumulation of polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated analogues (OH-PBDEs and MeO-PBDEs) in the blood of harbor porpoises, Dall's porpoises, and finless porpoises stranded or bycaught in Japanese coastal waters and in the North Pacific Ocean. Moreover, we suggested the origins of these contaminants and the factors affecting their pattern of accumulation. Levels of PBDEs in Dall's porpoises were one order of magnitude greater than those in the other species. OH-PBDE and MeO-PBDE levels were comparable to those of PBDEs. However, no correlation was found between the levels of OH-PBDEs and PBDEs, whereas a strong correlation was found between that of OH-PBDEs and MeO-PBDEs (p &lt; 0.001). 6OH-BDE47, reported compound bio-synthesized by marine low-trophic level organisms, was the dominant congener. These results suggest that PBDEs found in these porpoise species derive from flame retardants, but OH-PBDEs and MeO-PBDEs are mainly of natural origins. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marenvres.2016.11.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of chemicals. Previous studies showed that Felidae and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous (eg, estrogens, androgens, and bile acids) and exogenous compounds (opioids, non-steroidal anti-inflammatory drugs, and environmental pollutants). However UGT2B activity and genetic background are unknown in carnivore species. Therefore, this study was performed to elucidate the species differences of UGT2Bs. Using typical substrates for UGT2Bs, UGT activity was measured in vitro. In addition, UGT2B genetic features are analyzed in silico. Results of UGT activity measurement indicate marked species differences between dogs and other carnivores (cats, Northern fur seals, Steller sea lions, Harbor seals, and Caspian seals). Dogs have very high V-max/K-m toward estradiol (17-glucuronide), estrone, lorazepam, oxazepam, and temazepam. Conversely, cats and pinniped species (especially Caspian seals and Harbor seals) have very low activities toward these substrates. The results of genetic synteny analysis indicate that Felidae and pinniped species have very small numbers of UGT2B isozymes (one or none) compared with dogs, rodents, and humans. Furthermore, Felidae species have the same nonsense mutation in UGT2B, which suggests that Felidae UGT2B31-like is also a pseudogene in addition to UGT1A6. These findings of lower activity of UGT2B suggest that Felidae and some pinniped species have very low UGT activity toward a wide range of chemicals. These results are important for Felidae and Pinnipedia species that are frequently exposed to drugs and environmental pollutants.

DOI： 10.1093/toxsci/kfx072

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Language：Japanese   Publisher：(一社)日本毒性学会  

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Language：Japanese   Publisher：(一社)日本毒性学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

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.

DOI： 10.1021/acs.est.7b01262

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We examined the secondary production of halogenated derivatives of polycyclic aromatic hydrocarbons (PAHs) in surface seawater. Pyrene was selected as the model compound and exposed to UV irradiation in synthetic seawater for various irradiation times. Pyrene underwent rapid photochemical reactions that produced various halogenated derivatives including 1-chloropyrene, 1-bromopyrene, three unidentified dichloropyrenes, and three unidentified bromochloropyrenes. The production of 1-chloropyrene (220-360 nM) was higher than that of 1-bromopyrene (7.3-12 nM), reflecting the high chlorine content of seawater. A pilot field survey was conducted to test the environmental implications of these results, and fresh, brackish, and seawater samples were collected in southwestern Japan. The variation in the concentration ratios between 1-chloropyrene and pyrene implied the presence of a specific source of 1-chloropyrene in coastal water, which can be partly explained by the secondary production observed in our photolysis experiments. In sum, the photochemical reactions of PAHs are a potential secondary source of halogenated PAHs, especially in marine environments heavily contaminated with PAHs. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2016.12.044

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

There are growing concerns about the increase in hyperthyroidism in pet cats due to exposure to organo-halogen 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 (60H-/MeO-BDE47 and 2'OH-/MeO-BDE68) from marine organisms. In particular, higher concentrations of 60H-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 60H-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 60H-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.

DOI： 10.1021/acs.est.5b04216

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

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 silica 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 CI-unsubstituted carbon of docked PCBs to the heme Fe in CYP2A and 2B.

DOI： 10.1021/acs.est.5b03890

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

There are various interspecies differences in xenobiotic-metabolizing enzymes. It is known that cats show slow glucuronidation of drugs such as acetaminophen and strong side effects due to the UGT1A6 pseudogene. Recently, the UGT1A6 pseudogene was found in the Northern elephant seal and Otariidae was suggested to be UGT1A6-deficient. From the results of measurements of uridine diphosphate-glucuronosyltransferase (UGT) activity using liver microsomes, the Steller sea lion, Northern fur seal, and Caspian seal showed UGT activity toward 1-hydroxypyrene and acetaminophen as low as in cats, which was significantly lower than in rat and dog. Furthermore, UGT1A6 pseudogenes were found in Steller sea lion and Northern fur seal, and all Otariidae species were suggested to have the UGT1A6 pseudogene. The UGT1 family genes appear to have undergone birth-and-death evolution based on a phylogenetic and synteny analysis of the UGT1 family in mammals including Carnivora. UGT1A2-1A5 and UGT1A7-1A10 are paralogous genes to UGT1A1 and UGTA6, respectively, and their numbers were lower in cat, ferret and Pacific walrus than in human, rat, and dog. Felidae and Pinnipedia, which are less exposed to natural xenobiotics such as plant-derived toxins due to their carnivorous diet, have experienced fewer gene duplications of xenobiotic-metabolizing UGT genes, and even possess UGT1A6 pseudogenes. Artificial environmental pollutants and drugs conjugated by UGT are increasing dramatically, and their elimination to the environment can be of great consequence to cat and Pinnipedia species, whose low xenobiotic glucuronidation capacity makes them highly sensitive to these compounds.

DOI： 10.1093/toxsci/kfv144

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

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 (BAF(plasma) = 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 BAF(plasma) 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.

DOI： 10.1021/acs.est.5b02478

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

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 (T-4) 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. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.envres.2015.02.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

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 300 pg g(-1) wet wt, respectively) than those in the serum of donors from the rural site (median: 290, 82, 230, and 200 pg g(-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 20 pg g(-1) wet wt, respectively) than in those from the e-waste recycling site (median: 43 and 0.52 pg g(-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. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.envres.2015.01.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

This study aimed to investigate the behavior of organic ultraviolet (UV) filters released by recreational activities along the Japanese coastline. Seasonal variations of organic UV filters in seawater were investigated at four different recreational beaches (Mogushi, Wakamiya, Tsurugahama, and Otachimisaki beaches) in both summer (July through August) and winter (December). Moreover, short time scale diurnal changes were monitored at Otachimisaki beach in summer. Of the four sunscreen agents tested in this study, two agents-2-ethylhexyl-4-methoxycinnamate (EHMC) and 2-ethylhexyl salicylate (EHS)-were detected in all samples, whereas octyl-dimethyl-p-aminobenzonic acid and 3-(4-methylbenzylidene)-camphor were lower than detection limits. In particular, EHMC, one of the most popular organic UV filters, was dominant. The highest concentration of EHMC was observed at 1,080 ng L-1, a level that exceeds those of previous studies. Both EHMC and EHS concentrations showed significant (p &lt; 0.05) seasonal variations with advancing summer suggesting direct input from recreational activities. The subsequent examination showed short time scale diurnal changes of organic UV filters on the beach. The results showed that diurnal changes in EHMC concentrations were correlated to the number of bathers. EHMC concentrations increased during the afternoon and decreased during the night, although complete attenuation during the night did not occur. EHMC persists along the coast due to low mobility and may persist the next day. This is the first study to show the natural attenuation behavior of organic UV filters along recreational beaches.

DOI： 10.1007/s00244-014-0106-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We have previously demonstrated that Baikal seals (Pusa sibirica) are still being exposed to polychlorinated biphenyls (PCBs), and the population is at risk. In the present study, we measured the residue levels of PCBs and their hydroxylated metabolites (OH-PCBs) in the blood of Baikal seals and assessed the impact of OH-PCBs on the thyroid function. Blood concentrations of PCBs and OH-PCBs were in the range of 2.8130 ng g(-1) wet wt. and 0.71-4.6 ng g(-1) wet wt., respectively. Concentrations of higher-chlorinated OH-PCBs (hexa- to octa-PCBs) were more than 70% to total OH-PCB concentrations, indicating Baikal seals are mostly risked by higher-chlorinated OH-PCBs. High levels of 4OH-CB146 and 4OH-CB187 and low levels of 4OH-CB107/4'OH-CB108 found in Baikal seals were different from those in other phocidae species, suggesting the unique drug-metabolizing enzyme activities and/or contamination sources in this species. Concentrations of some OH-PCBs in males were significantly higher than those in females. These results suggest that these isomers may be preferentially transferred from mother to pup via cord blood. However, concentrations of almost all the isomers were not significantly correlated with the levels of blood total T3 and T4, implying less impact of PCB-related compounds on the thyroid hormone circulation. (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2014.03.089

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

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 (T-4) levels and the ratios of 3,3',5-triiodo-l-thyronine (T-3)/reverse 3,3',5'-triiodo-l-thyroninee (rT(3)). 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 T-3 and T-4 in the liver.

DOI： 10.1021/es5043386

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

In the present study, a sensitive and accurate isotope dilution method was developed for the simultaneous determination of 17 polar pharmaceutical and personal care product (PPCP) residues (logK(ow) = 1.40-5.74), including 14 pharmaceuticals and 3 personal care products, in biological organs and tissues. The proposed method involved enzymatic hydrolysis, followed by sequential clean-up using silica gel chromatography and gel permeation chromatography, and analysis via ultra-high-performance liquid chromatography with tandem mass spectrometry. This method yielded acceptable absolute recoveries (48-88%) and internal standard-corrected recoveries (90-130%) for 17 PPCPs. Method detection limits were between 0.0092 and 3.2 ng g(-1) wet weight, and the limits of quantification were between 0.020 and 8.7 ng g(-1) wet weight. The method can be used to readily detect the target compounds at trace levels while minimizing the required sample volume. The developed method was applied to the determination of 17 PPCPs in the liver and kidney of 17 birds collected from Japan and also in the plasma, liver, and brain of 7 cyprinoid fish from an effluent-dominated stream in Japan. Triclosan was detected in 5 of 11 fish-eating birds but not in non-fish-eating birds, suggesting the contamination of prey fish by the chemical. Non-steroidal anti-inflammatory drugs, antibacterial agents, and psychotropic agents were frequently detected in the fish tissues. In addition, 7 of the target compounds were found in fish brain. The median brain/plasma ratios of the psychotropic agents ranged from 1.6 (carbamazepine) to 12 (diphenhydramine), indicating high transportability to fish brain. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.chroma.2014.06.016

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Language：Japanese   Publisher：日本毒性学会  

【はじめに】北海道では、猛禽類において鉛弾摂取による鉛中毒が問題となっている。現在は鉛弾の使用規制が設けられているものの、未だに被害個体が発見されている。また、本州など他地域でも鉛中毒個体が発見されているが、北海道を除く地域における汚染実態調査は極僅かであり、鉛弾使用規制も不十分である。そこで、本研究では北海道、本州、四国において死亡した猛禽類の鉛濃度と鉛安定同位体比を測定し、鉛汚染状況と汚染源の解明を試みた。&lt;br&gt;【方法】試料は、1993年から2014年に北海道、本州、四国で死亡したイヌワシ、トビ、オオワシ、オオタカ、フクロウ、オジロワシ、オオハヤブサ、クマタカ、サシバ、ハイタカ、ツミ、チョウゲンボウの計49個体の肝臓を採取し、誘導結合プラズマ質量分析計で鉛濃度と鉛安定同位体比（&lt;sup&gt;207&lt;/sup&gt;Pb/&lt;sup&gt;206&lt;/sup&gt;Pb、&lt;sup&gt;208&lt;/sup&gt;Pb/&lt;sup&gt;206&lt;/sup&gt;Pb）を分析した。&lt;br&gt;【結果と考察】本研究の結果、1999‐2014年に北海道で死亡した4羽のオオワシにおいて、鉛中毒が疑われる値（11.0-29.5 mg/kg、湿重量）が検出された。北海道では2004年に大型獣の狩猟における鉛弾使用が禁止されているが、2013、2014年に採取されたオオワシにおいても高濃度の鉛蓄積が検出され、このうち1羽からはレントゲン撮影と剖検で胃内に鉛弾の破片が認められた。また岩手県で死亡したイヌワシからも高濃度の鉛蓄積（2.0 mg/kg）が認められた。さらに鉛安定同位体比を分析した結果、高濃度の鉛蓄積個体の鉛安定同位体比の値が同程度であった。このうち1羽から鉛弾が検出されたことを考慮すると、これらの高濃度蓄積個体の汚染源は鉛ライフル弾であると考えられた。&lt;br&gt; 上記の結果から、猛禽類の鉛弾摂取による中毒が未だに問題となっていることが明らかとなった。従って、北海道以外の地域における調査、また日本全国における鉛弾流通の完全禁止など規制強化の検討が必要であると考えられた。

J-GLOBAL

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Language：Japanese   Publisher：日本毒性学会  

【目的】グルクロン酸抱合酵素(UGT)は、異物代謝の第Ⅱ相抱合反応を担い、各動物の化学物質感受性決定に関与することが報告されている。食肉目ネコ亜目(&lt;i&gt;Feliformia&lt;/i&gt;)では環境化学物質や薬物等の代謝に関与するUGT1A6の偽遺伝子化が報告されており、この偽遺伝子化によりアセトアミノフェン等の薬物の毒性作用が強く表れることが知られている。一方、食肉目に属する鰭脚類(&lt;i&gt;Pennipedia&lt;/i&gt;)では、PCB、DDTなどの残留性有機汚染物質の高濃度蓄積が報告されているが、感受性に関与するUGTについての研究がほとんど行われていない。そこで、鰭脚類を中心とした食肉目において、UGTの機能解析及び系統解析を行い、種差を明らかにすることを目的とした。&lt;br&gt;【方法】食肉目に属するネコ(&lt;i&gt;Felis catus&lt;/i&gt;)、イヌ(&lt;i&gt;Canis familiaris&lt;/i&gt;)、鰭脚類であるトド(&lt;i&gt;Eumetopias jubatus&lt;/i&gt;)、キタオットセイ(&lt;i&gt;Callorhinus ursinus&lt;/i&gt;)、カスピカイアザラシ(&lt;i&gt;Phoca caspica&lt;/i&gt;)及び対照としてラット(&lt;i&gt;Rattus norvegicus&lt;/i&gt;)の肝臓ミクロソームを調整した。この肝臓ミクロソームを用いて、1-ヒドロキシピレンを基質としてUGT活性を測定した。さらに食肉目UGT1A遺伝子について、他の哺乳類と比較し、系統解析を行った。&lt;br&gt;【結果及び考察】1-ヒドロキシピレンを基質として用いたところ、イヌはラットと同程度のUGT活性を示したが、鰭脚類3種およびネコのUGT活性はラットの3分の1以下だった。また、UGT1A遺伝子は一般に2-10程度のホモログが近接して染色体上に存在しているが、系統解析及びシンテニー解析より、食肉目は齧歯目に比べUGT1A領域が短くUGT1A分子種数が少ないことが確認された。さらに、トドおよびキタオットセイでは、UGT1A6のエクソン1領域に2塩基挿入によるストップコドンが生じ、偽遺伝子化していることが明らかになった。以上の結果より、鰭脚類は、UGTによる異物代謝能が低く、環境化学物質に対する感受性が高い可能性が考えられた。

J-GLOBAL

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Language：Japanese   Publisher：日本毒性学会  

【目的】グルクロン酸抱合酵素(UGT)は、生体外異物代謝の第Ⅱ相抱合反応を担い、各動物の化学物質感受性決定に関与することが報告されている。食肉目ネコ亜目(Feliformia)では環境化学物質や薬物等の代謝に関与するUGT1A6の偽遺伝子化が報告されており、この偽遺伝子化に伴いアセトアミノフェン等の薬物の毒性作用が強いことが知られている。一方、食肉目に属する鰭脚類(Pinnipedia)では、環境化学物質の高濃度蓄積が報告されているが、感受性に関与するUGTについての研究はほとんど行われていない。そこで、鰭脚類を中心とした食肉目において、肝臓でのUGT活性の測定と系統解析を行った。&lt;br&gt;【方法】食肉目に属するネコ(&lt;i&gt;Felis catus&lt;/i&gt;)、イヌ(&lt;i&gt;Canis familiaris&lt;/i&gt;)、鰭脚類であるトド(&lt;i&gt;Eumetopias jubatus&lt;/i&gt;)、キタオットセイ(&lt;i&gt;Callorhinus ursinus&lt;/i&gt;)、カスピカイアザラシ(&lt;i&gt;Phoca caspica&lt;/i&gt;)及び対照としてラット(&lt;i&gt;Rattus norvegicus&lt;/i&gt;)の肝臓ミクロソームを作成し、1-ヒドロキシピレン(UGT1A6、UGT1A7、UGT1A9)、アセトアミノフェン(UGT1A1、UGT1A6、UGT1A9)、セロトニン(UGT1A6)を基質としてUGT活性を測定した。また、NCBIのデータベースからUGT1A領域の系統解析およびシンテニー解析を行った。&lt;br&gt;【結果及び考察】1-ヒドロキシピレン、アセトアミノフェン、セロトニンに対するUGT抱合活性を測定した結果、ラットに比べ食肉目では極めて低い活性を示した。また、系統解析及びシンテニー解析より、解析した全ての食肉目において、UGT1A分子種は特徴的な2遺伝子であるUSP40 とMROH2の間に保存されていることが明らかになった。さらに、食肉目は齧歯目に比べUGT1A領域が短く、UGT1A分子種数が少ないことが確認された。以上の結果から、鰭脚類を含めた食肉目はUGTによる異物代謝能が低く、環境化学物質に対する感受性が高い可能性が考えられた。

J-GLOBAL

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Information on accumulation of halogenated phenolic contaminants in the blood of marine mammal is limited. The present study, we determined the residue levels and patterns of chlorinated and brominated phenolic contaminants (OH-PCBs, OH-PBDEs and bromophenols) in the blood collected from pinnipeds (northern fur seal, spotted seal, Steller sea lion and ribbon seal) and small cetaceans (harbor porpoise and Dall's porpoise) from Japanese coastal waters. Concentrations of PCBs and OH-PCBs found in pinnipeds were the same as in small cetaceans living in the same coastal area. However, significantly lower concentrations of brominated compounds (PBDEs, MeO-PBDEs, OH-PBDEs) were found in the blood of pinnipeds than the levels found in cetacean species which live same area (p &lt; 0.05). This difference of accumulation pattern suggested pinnipeds have an enhanced capability to degrade organobromine compounds relative to cetaceans. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.marenvres.2013.08.016

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In this study, we developed a comprehensive, highly sensitive, and robust method for determining 53 congeners of three to eight chlorinated OH-PCBs in liver and brain samples by using isotope dilution gas chromatography (GC) coupled with electron capture negative ionization mass spectrometry (ECNI-MS). These results were compared with those from GC coupled with electron ionization high-resolution mass spectrometry (El-HRMS). Clean-up procedures for analysis of OH-PCBs homologs in liver and brain samples involve a pretreatment step consisting of acetonitrile partition and 5% hydrated silica-gel chromatography before derivatization. Recovery rates of tri- and tetra-chlorinated OH-PCBs in the acetonitrile partition method followed by the 5% hydrated silica-gel column (82% and 91%) were higher than conventional sulfuric acid treatment (2.0% and 3.5%). The method detection limits of OH-PCBs for each matrix obtained by GC/ECNI-MS and GC/EI-HRMS were 0.58-2.6 pg g(-1) and 0.36-1.6 pg g(-1) wet wt, respectively. Recovery rates of OH-PCB congeners in spike tests using sample matrices (10 and 50 pg) were 64.7-117% (CV: 4.7-14%) and 70.4-120% (CV: 2.3-12%), respectively. This analytical method may enable the simultaneous detection of various OH-PCBs from complex tissue matrices. Furthermore, this method allows more comprehensive assessment of the biological effects of OH-PCB exposure on critical organs. (C) 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.talanta.2013.10.031

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The present study investigated polychlorinated biphenyls (PCBs) and hydroxylated metabolites of PCBs (OH-PCBs) in blood from three porpoise species: finless porpoises (Neophocaena phocaenoides), harbor porpoises (Phocoena phocoena), and Dall's porpoises (Phocoenoides dalli). The porpoises were found stranded or were bycaught along the Japanese coast. Concentrations of OH-PCB were the highest in Dall's porpoises (58 pg g(-1) wet wt), second highest in finless porpoises (20 pg g(-1) wet wt), and lowest in harbor porpoises (8.3 pg g(-1) wet wt). The concentrations in Dall's porpoises were significantly higher than the concentrations in finless porpoises and harbor porpoises (p &lt; 0.05 and p &lt; 0.01, respectively). There was a positive correlation between PCB and OH-PCB concentrations (r = 0.67, p &lt; 0.001), suggesting the possible concentration-dependent induction of CYP enzymes. The three porpoise species may have exceptionally low metabolic capacities compared with other marine and terrestrial mammals, because low OH-PCB/PCB concentration ratios were found, which were 0.0016 for Dall's porpoises, 0.0013 for harbor porpoises, and 0.00058 for finless porpoises. Distinct differences in the OH-PCB congener patterns were observed for the three species, even though they are taxonomically closely related. (c) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2013.04.024

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

In this study, we hypothesize that natural photochemical reactions of polycyclic aromatic hydrocarbons (PAHs) in tidal flats are responsible for the occurrence of chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs). This study aims to survey the impact of photochemical reactions using a combination of field surveys and lab-scale experiments. Concentrations and profiles of PAHs and Cl-PAHs in road dust and sediments collected from seven tunnels and two watersheds, respectively, were determined. In the lab-scale experiments, anthracene was irradiated with ultraviolet (UV) light under various salinity conditions. No detectable Cl-PAHs were found in the road dust. However, Cl-PAHs were detected in the sediments from 700 to 6.1 x 103 pg g-1 and speClfically from downstream sites. 2-Monochloroanthracene (2-Cl-ANT) and 9,10-dichloroanthracene (9,10-di-Cl-ANT) were dominant in the sediments. In the IDomen River watershed, the Sigma Cl-PAHs and the salinity showed a significant positive correlation (p &lt; 0.01) in the sediments, while such a correlation was not found for PAHs. 2-Cl-ANT, 9-monochloroanthracene, and 9,10-di-Cl-ANT were identified as transformation products in the UV irradiation experiments. Production of these Cl-PAHs was dependent on the solution salinity. These results support our hypothesis, and we conclude that photochemical reactions significantly contribute to the occurrence of Cl-PAlis in the studied tidal flats.

DOI： 10.1021/es3044483

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Selected six kinds of polycyclic aromatic hydrocarbons (PAHs) (naphthalene: NA, phenanthrene: (PHE), anthracene (ANT), fluoranthene (FLR), pyrene (PYR), and benzo[a]pyrene (B[a]P)) were exposed to natural sunlight under simulated tidal flat conditions, to check possibilities for photochemical productions of halogenated derivatives in the coastal environment. Moreover, 11 molecular descriptors were derived based on PM6 Hamiltonian for each PAH. Photochemical reaction induced productions of various 13 kinds of halogenated derivatives, which include 7 unknown products. In the determined 6 halogenated derivatives, the highest production amount was 6-chlorobenzo[a]pyrene. Moreover, PYR showed the behavior that produced halogenated derivatives significantly higher than its structural isomer of FLR. After the determination of production amounts, correlation between the production amounts of halogenated derivatives and the molecular descriptors of individual PAHs were examined. The energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital (E-HOMOLUMO), which is a measure of chemical stability, showed the strongest significance (p &lt; 0.01) and give enough explanation for differences in the production amounts among structural isomers. PAHs that have small E-HOMOLUMO showed high potential to produce halogenated derivatives. ANT, PYR and B[a]P would have potentially high capability to induce halogenated derivatives in the coastal environment. We further discussed the impact of photochemical reaction on environmental fate of PAHs and halogenated PAHs. Congener profiles observed in our previous field surveys seemed to suggest contributions of photochemical reaction to occurrences of Cl-PAHs.

DOI： 10.1080/10406638.2013.770406

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Residue levels and patterns of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), their hydroxylated metabolites (OH-PCBs, OH-PBDEs), and methoxylated PBDEs (MeO-PBDEs) in the blood of various terrestrial mammals in Japan, including cats, raccoon dogs, dogs, masked palm civets, foxes, raccoons, badgers, and mongooses were determined. Tri- through penta-chlorinated OH-PCBs were predominant in cat blood, whereas hexa- through octa-chlorinated OH-PCBs were found in other species. High proportion of BDE209 was found in all species, suggesting exposure to municipal waste and soil containing higher levels of deca-BDE products. 6OH-/MeO-BDE47 and 2'OH-/MeO-BDE68 were dominant in all terrestrial mammals. This is first report on the detection of OH-/MeO-PBDEs in the blood of terrestrial mammals. High concentrations of OH-/MeO-PBDEs were found in cats, suggesting the intake of these compounds from seafood. Cats exhibited higher accumulation and specific patterns of OH-PCBs, OH-PBDEs, and MeO-PBDEs, they may be at a high risk from these metabolites. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2012.11.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We determined the contamination status and accumulation profiles of polychlorinated biphenyls (PCBs), hydroxylated PCB congeners (OH-PCBs), polybrominated diphenyl ethers (PBDEs), hydroxylated PBDEs (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs), and bromophenols (BPhs) in serum from e-waste recycling workers and residents near a coastal area in India. Residue levels of penta- to octa-chlorinated PCBs, penta- to octa-chlorinated OH-PCBs, 6MeO-BDE47, 6OH-BDE47, and 2,4,6-tri-BPh in serum from residents living near the coastal area were significantly higher than those in serum from e-waste recycling workers. Residue levels of tri- to tetra-chlorinated PCBs, tri- to tetra-chlorinated OH-PCBs. PBDEs. octa-brominated OH-PBDEs, and tetra-BPhs in serum from e-waste recycling workers were higher than those in serum from residents living near the coastal area. Principal component analysis revealed that residents living near the coastal area and e-waste recycling workers had different serum profiles of chlorinated and brominated compounds. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envint.2012.05.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Land application of recycled manure produced from biosolids and reclaimed wastewater can transfer pharmaceutical chemicals to terrestrial environments, giving rise to potential accumulation of these residues in edible plants. In this study, the potential for plant uptake of 13 pharmaceutical chemicals, and the relation between the accumulation features within the plant and the physicochemical properties were examined by exposing pea and cucumber to an aqueous solution containing pharmaceutical chemicals. Ten of 13 compounds tested were detected in plant leaves and stems. Comparison of the plant uptake characteristics and the octanol water partition coefficient of pharmaceutical chemicals showed that compounds with an intermediate polarity such as carbamazepine and crotamiton could be easily transported to plant shoots. Moreover, these results suggest the possibility of highly hydrophilic pharmaceutical chemicals such as trimethoprim and sulfonamides to be accumulated in plant roots owing to their low permeability in root cell membranes.

DOI： 10.1021/jf303142t

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

This study investigated environmental distributions and production mechanisms of chlorinated polycyclic aromatic hydrocarbons (CI-PAHs) in the sediments from some tidal flats located in Asia. CI-PAHs were found in sediments taken from Arao tidal flat, Kikuchigawa River and Shirakawa River. The range of Sigma CI-PAHs was from 25.5 to 483 pg g(-1) for Kikuchigawa River and Arao tidal flat, respectively.
Concentrations of PAHs and CI-PAHs showed no significant correlations (r = 0.134). This result suggests that the origins of these compounds differ. In the identified CI-PAH isomers, the most abundant CI-PAH isomer was 9,10-dichloroanthracene (9,10-di-CI-ANT) in the three sites. In general, concentrations of CI-ANTs in the coastal environment are about 3-5 orders of magnitude lower than those of anthracene (ANT). However, concentration ratios between CI-ANTs and ANT (CI-ANTs/ANT) in the sediments ranged from 4.1% to 24.6%. This result indicated that CI-PAHs were not generated under industrial processes but the high concentration ratios have resulted from the contribution of photochemical production of CI-ANTs in the sediments because ANT is known to have high photochemical reactivity.
For examining this phenomenon, ANT adsorbed onto glass beads was irradiated with UV under the mimicked field conditions of tidal flats. As a result, it was noticed that, while chlorinated derivatives were negligible in a light-controlled group, production of 2-CI-ANT, 9-CI-ANT and 9,10-diCI-ANT on the irradiated surface were found in this study. These results suggest that photochemical reaction of PAHs can be a potential source of the occurrence of CI-PAHs in the coastal environment. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2012.03.017

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Proceedings

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Proceedings

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Proceedings

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Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Books

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

We determined the residue levels and patterns of hydroxylated polybrominated diphenyl ethers (OH-PBDEs), and related compounds, such as PBDEs, methoxylated PBDEs (MeO-PBDEs), and bromophenols (BPhs) in the blood of eleven cetacean species stranded along the Japanese coasts. The dominant OH- and MeO-PBDE isomers found in all cetaceans were 6OH-BDE47 and 6MeO-BDE47. Additionally, 2,4,6-triBPh was dominant isomer in all cetaceans. In contrast, specific differences in the distribution of para- and meta- OH-PBDE isomers and some BPhs (potential PBDEs metabolites) were found among the cetaceans.
Residue levels of Sigma MeO-PBDEs and 6OH-BDE47 + 2'OH-BDE68, and 2,4,6-triBPh and 6OH-BDE47 + 2'OH-BDE68 showed a significant positive correlation. These results may suggest that the large percentages of OH-PBDEs, MeO-PBDEs and 2,4,6-triBPh might share common source (i.e. biosynthesis by marine organisms), or metabolic pathway in cetacean species. Significant correlations were found between the concentrations of BDE99 and 2,4,5-triBPh. This result suggested that 2,4,5-triBPh in cetaceans could be a metabolite of BDE99. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2011.08.035

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

The present study measured the concentrations of 25 elements (Li, Mg, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Ag, Cd, In, Sn, Sb, Cs, Ba, Hg, Tl, Pb and Bi) in the whole body of Isaza which is an endemic fish species to Lake Biwa, Japan, and compared the values in the specimens from the mass mortality Isaza (MMI) and normal fresh Isaza (NFI). The mean levels of Mn and total As (T-As) were relatively higher in MMI than in NFI. In the T-As, highly toxic inorganic As was detected in MMI. Moreover we found Mn and As concentrations in surface sediment were extremely high and temporally increased. From all these results, we could infer that the dissolution of Mn and As from surface sediment of Lake Biwa might have been one of the cause for the mass mortality of Isaza. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.envpol.2011.05.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Information on accumulation of polychlorinated biphenyl metabolites (OH-PCBs) and hydroxylated polybrominated diphenyl ethers (OH-PBDEs) in the blood of marine fish is limited. The present study, we determined the residue levels and patterns of PCBs, OH-PCBs, PBDEs, OH-PBDEs and methoxylated PBDEs (MeO-PBDEs) in the blood collected from scalloped hammerhead shark (Sphyrna lewini) and Japanese amberjack (Seriola quinqueradiata), species of predatory fish at Japanese coastal waters. The predominant homologues found in Japanese amberjacks were mono- and di-chlorinated OH-PCBs, and scalloped hammerhead sharks were octa-chlorinated OH-PCBs. The predominant OH-PCB isomers were lower-chlorinated OH-PCBs such as 6OH-CB2 and 2&apos;OH-CB9 in Japanese amberjacks. This result suggests that exposure of Japanese amberjacks to lower-chlorinated OH-PCBs might be from the ambient aquatic environment. In scalloped hammerhead sharks, 4,4&apos;diOH-CB202, 4OH-CB201 and 4OH-CB146 were the predominant isomers accounting for approximately 60% of the total OH-PCBs.
The predominant MeO-PBDE isomers were 6MeO-BDE47 followed by 2&apos;MeO-BDE68 in both species. As for OH-PBDE isomers, 6OH-BDE47 was predominant followed by 2&apos;OH-BDE68 in Japanese amberjacks and scalloped hammerhead sharks. Residue levels of Sigma MeO-PBDEs and Sigma OH-PBDEs showed a significant positive correlation (p = 0.029). This result suggests that MeO-PBDEs and OH-PBDEs share a common source or a metabolic pathway in fishes. Characteristic differences found in the profiles of OH-PCBs and OH-PBDEs in Japanese amberjack and scalloped hammerhead shark show the need for further studies on the differences in exposure profiles, metabolic capacities and toxic effects in fish. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2011.06.092

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

In recent years, sludge generated in sewage treatment plants (STPs) and solid waste from livestock being utilized is useful for circulation of nourishment in farmlands as recycled organic manure (ROM). In this study, we determined the residue levels and patterns of 12 pharmaceutical products generated by human activity in the ROMs produced from human waste sludge (HWS), sewage sludge (SS), cattle manure (CM), poultry manure (PM), swine manure (SM) and horse manure (HM).
The kind and number of pharmaceutical products detected in ROMs were different. Fluoroquinolones (FQs) were detected at high levels in HWS and SS samples. In addition, the detection frequency and concentration levels of sulfonamides (SAs) in PM and SM were high. Moreover, high concentrations of chlortetracycline (CTC) were found in only SM. These differences reflect specific adherence adsorption of the pharmaceutical products to different livestock and humans. Moreover, it was found that the concentrations of pharmaceutical products and fermentation levels of ROMs had significant positive correlation (r = 0.41, p = 0.024).
When the fermentation test of ROM was conducted in a rotary fermentor in a lab scale test, the residue levels of pharmaceutical products decreased effectively except carbamazepine (CBZ). The rates of decrease were in the case of tetracyclines (TCs): 85-92%, FQs: 81-100%, erythromycine: 67%, SAs: 79-95%, trimethoprim: 86% and CBZ: 37% by 30 d. Pharmaceutical products that can be decomposed by fermentation process at the lowest impact of residual antibiotic activities may therefore be considered as environmentally friendly medicines. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2011.03.048

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The photodegradation pathways of 2-(2,4-dichlorophenoxy)-5-chlorophenol (triclosan) in water were studied. The main purposes were to identify structures of intermediates derived by radical reaction using TiO2 advanced oxidation processes and to evaluate the endocrine disrupting activities in treated triclosan during oxidative reactions. Intermediates such as dichlorophenols, 2,8-dibenzo-p-dioxin, tetrachlorinated diphenyl ether (tetraclosan) and hydroxylated triclosan were produced by photoreaction. The estrogen, thyroid hormone and retinoid X receptor activities of the treated triclosan were measured with the yeast two-hybrid assay. It was found that tetraclosan and 2,4-dichlorophenol have stronger thyroid hormone activities than triclosan in the presence of S9.

DOI： 10.1007/s00128-011-0249-4

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In this study, we determined the residue levels and patterns of polychlorinated biphenyls (PCBs) and hydroxylated PCBs (OH-PCBs) in the blood from eight species of toothed whales and three species of baleen whales stranded along the Japanese coast during 1999-2007. Penta- through hepta-chlorinated PCB congeners were the dominant homologue groups in all cetaceans. In contrast, specific differences in the distribution of dominant OH-PCB isomers and homologues were found among the cetacean species. In five species of toothed whales (melon-headed whale, Stejneger's beaked whale, Pacific white-sided dolphin, Blainville's beaked whale, and killer whale), the predominant homologues were OH-penta-PCBs followed by OH-tetra-PCBs and OH-tri-PCBs. The predominant homologues of finless porpoise and beluga whale were OH-penta-PCBs followed by OH-hexa-PCBs and OH-tri-PCBs. The predominant OH-PCB isomers were para-OH-PCBs such as 4'OH-CB26, 4'OH-CB25/4'OH-CB26/4OH-CB31, 4OH-CB70, 4'OH-CB72, 4'OH-CB97, 4'OH-CB101/4'OH-CB120, and 4OH-CB107/4'OH-CB108 in toothed whales. In three baleen whales (common minke whale, Bryde's whale, and humpback whale) and in sperm whale (which is a toothed whale), OH-octa-PCB (4OH-CB202) was the predominant homologue group accounting for 40-80% of the total OH-PCB concentrations. The differences in concentrations and profiles of OH-PCBs may suggest species-specific diets, metabolic capability, and the transthyretin (TTR) binding specificity. These results reveal that the accumulation profiles of OH-PCBs in cetacean blood are entirely different from the profiles found in pinnipeds, polar bear, and humans.

DOI： 10.1021/es1003928

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In the present study, we analyze and characterize the levels of PCBs and OH-PCBs in serum and breast adipose tissue, and measure TH (total 3,5,5&apos;-triiodothyronine (tT3) and total L-thyroxine (tT4)) levels in serum of Japanese women diagnosed with breast cancer (n = 51) to know how PCBs affect thyroid hormone homeostasis. Concentrations of Sigma(90)OH-PCBs in serum and adipose tissues were 630 pg g(-1) serum wet wt. and 140 pg/g(-1) lipid wt., respectively, and the levels of OH-PCBs in adipose tissues were 4-5 times lower than in serum. The tT3 and tT4 concentrations in serum (n = 20) were 1.3 ng g(-1) serum wet wt. and 62 ng g(-1) serum wet wt., respectively. Among all the OH-PCBs, 4&apos;-OH-CB101/120, 4-OH-CB107/4&apos;-OH-CB108, 3&apos;-OH-CB138, 4-OH-CB146, 3-OH-CB153, 4&apos;-OH-CB172, and 4-OH-CB187 were the dominant isomers in serum. No significant correlation between the concentrations of the TH and OH-PCBs in serum was observed (p &gt; 0.05). The results indicated that the relationship between the OH-PCB levels and the thyroid hormone markers was rare. From analysis of two kinds of human biological samples, it was estimated that OH-PCBs have little effect on thyroid hormone homeostasis.

DOI： 10.1021/es9012432

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Vitellogenin (VTG)-inducing activities of 21 kinds of hydroxylated polychlorinated biphenyls (OH-PCBs) were investigated by an assay system using the primary-cultured hepatocyte of the adult male Xenopus laevis. An enzyme-linked immunoabsorbent assay (ELISA) was able to detect VTG at a minimum detection limit of 0.2 ng mL(-1). The levels of VTG production in hepatocytes of male X laevis exposed to six kinds of OH-PCB isomers (2&apos;-OH-CB30, 3&apos;-OH-CB30, 4&apos;-OH-CB30, 4&apos;-CH-CB50, 4&apos;-OH-CB61 4&apos;-OH-CB65) were significantly higher as compared to the control group (p &lt; 0.05). The relative ranking of the OH-PCBs was E2 (100%), 4&apos;-OH-CB30 (2.0%) &gt; 2&apos;-OH-CB30 (0.15%) &gt; 4&apos;-OH-CB61 (0.046%) &gt; 3&apos;-OH-CB30 (0.013%) &gt; 4&apos;-OH-CB50 (0.002%) &gt; 4&apos;-OH-CB65 (0.0001%). Although there were some differences between the estrogenicity values by the VTG-inducing activities and yeast two-hybrid assay for human estrogen receptor alpha (ER alpha).
The results from VTG-assays suggested that an important factor for determining estrogenicity is the positions of the hydroxyl group and chlorine with the highest activity resulting from a para-hydroxyl group. The OH-PCB structures of high rank order in the VTG-assay had no chlorine substituted phenolic ring. Moreover, the meta-chlorine substituted phenolic ring is an important factor in determining estrogenicity. The CH-PCBs with meta-chlorine substituted phenolic ring did not show estrogenicity during VTG-assay. (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2009.12.018

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The behavior of estrogens (estrone: E1, 17 beta-estradiol: E2, estriol: E3 and ethinylestradiol: EE2) and an androgen (testosterone) in the water and sludge from Johkasou in Japan was investigated. The concentrations of E1, E2, E3 and testosterone in water samples from the Johkasou were 33-500, N.D. similar to 150, N.D. similar to 6,700 and 500 ng/L, respectively. In sludge samples, the concentrations of E1, E2, E3, and testostrerone were N.D. similar to 39, N.D. similar to 6.7, N.D. similar to 60 and 0.2-9.0 ng/L, respectively. EE2 was not detected in all samples. The removal rates of E1, E2, E3 and testosterone in Johkasou were 45%-91%, 66%-100%, 90%-100%, and about 90%, respectively.

DOI： 10.1007/s00128-009-9755-z

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The oxidative photodegradation behaviors of selected three coplanar polychlorinated biphenyls (PCBs), (CB77, C1381, and C13169) 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 and thyroid hormonal activity in the treated three coplanar PCBs during the oxidative reactions.
Approximately 90% of the three coplanar PCBs decomposed within 180 min. Intermediates from the decomposition of the three coplanar PCBs, such as some hydroxylated-PCBs (OH-PCBs), 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 OHPCBs increased within 60 min of irradiation time.
The estrogenic activity and thyroid hormonal activity of the intermediates from the three coplanar PCBs in water at 0, 60, 120, 180 and 240 min of irradiation time were assessed by using a yeast two-hybrid assay system for human estrogen receptor alpha (hER alpha) and human thyroid hormone receptor alpha (hTR alpha). The maximal estrogenic activities were induced by the solutions of decomposed PCBs with irradiation time at 60-120 min similar and slightly lower than those after the irradiation time. We found that the solutions occuring during the irradiation times of 60-120 min contained several 4-OH-PCBs substituted with OH and Cl at para- and para'-positions having estrogenic activity. The thyroid hormonal activity was not detected in the decomposed three coplanar PCBs solutions. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.chemosphere.2006.06.01

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The oxidative degradation behavior of bisphenol A (BPA) using titanium dioxide (TiO2) in water was investigated. The main purposes were to clarify the relationship with estrogenic activity from the degradation pathways demonstrated by oxidation of BPA in water. Approximately 99% of the BPA decomposed within 300 min, and gas chromatography (GC) mass spectrometry (MS) and liquid chromatography (LC) MS analysis revealed many intermediates during the degradation process. Intermediates by decomposition of BPA, such as hydroxylated-BPA (OH-BPA), carboxylic intermediates, phenolic intermediates, and other intermediates produced by the cleavage of a benzene ring were identified and quantified. Estrogenic activities of the degradation pathways of the BPA in water were assessed by using a constructed yeast two-hybrid assay system for human estrogen receptor alpha (hER alpha) and Japanese medaka fish (Oryzias latipes) estrogen receptor alpha (medER alpha). Estrogenic activity for hER alpha and medER alpha was reduced to less than 20% of the initial activity for BPA after 240 min of UV irradiation. However, estrogenic activity for medER alpha was increased by 110% from the initial activity for BPA at 60 min of UV irradiation. It was estimated that medER alpha assay was more sensitive for BPA and the intermediates than was the hER alpha assay. From these findings, we estimate that the intermediates by the oxidation of BPA have the behaviors of xenoestrogen to the aquatic wildlife in the environment.

DOI： 10.1007/s00244-005-0204-7

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In order to investigate the sources and carcinogenicity of polycyclic aromatic hydrocarbons (PAHs) in aerosol particles in the urban atmosphere of Kumamoto, Japan, atmospheric particles were collected by using two high volume air samplers at a roadside site and a residential site during December 2003 &sim; May 2004, and 16 major PAHs in the samples were analyzed with GC-MS. It was confirmed that the PAHs were mainly from diesel and gasoline engines as expected at both sites. At the roadside site, the total concentration of the 16 PAHs was 10.08 &sim; 99.12 ng m<SUP>-3</SUP> with the average 46.60 ng m<SUP>-3</SUP>. At the residential site it was 11.68 &sim; 60.93 ng m<SUP>-3</SUP> with the average 30.03 ng m<SUP>-3</SUP>, which is apparently smaller than that at the roadside site. However, the carcinogenicity of the particulate PAHs at the residential site was approximately at the same level as that at the roadside site. Benzo(b)fluoranthene (BbF) , Benzo(k)fluoranthene (BkF) and Dibenzo(a.h)anthracene (DahA) were the major contributors to the carcinogenicity. The concentration of DahA was much smaller than that of BbF and BkF at both sites, but it was considerably larger at the residential site than at the roadside site, which made the carcinogenicity at the residential site comparable to that at the roadside site.

DOI： 10.11203/jar.22.135

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Linear alkylbenzene sulfonate (LAS), an anionic surfactant, is considered to be an organic pollution source in rivers and lakes. It is known that the LAS discharged into the water environment gradually decomposes to sulfophenyl carboxylic acid (SPC) . We developed a simultaneous determination method for LAS and SPC by utilizing LC/ESI/MS, and applied the method to water and sediment samples taken from rivers, estuaries and tidal flats in Kumamoto. The concentration levels of LAS (C10-C14) and SPC (C7-C12) in the river were 70.6-254, μg/l and<2.49-81.9, μg/l, respectively. The LAS and SPC in the sediments were not detected at all or were found to be at very low levels. It was suggested that the residual tendency of LAS and SPC would be low.<BR>In regards to the eco-toxicological evaluation of LAS and SPC using a yeast two-hybrid assay, neither LAS nor SPC had estrogenic activity. As the result of YTOX test, EC<SUB>20</SUB> of LAS was from 30 to 60 times as low as that of SPC.

DOI： 10.5985/jec.16.239

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Environmental Chemistry  

The estrogen and androgen in the compost produced from sewage sludge and solid waste of livestock were investigated in twenty-six kinds of composts which were sold on the open market.<BR>Estrone (E1) was detected in all kinds of composts. 17β-estradiol (E2) was detected in twenty-one kinds of composts, and estriol (E3) was detected in one kind of compost. Ethynylestradiol (EE2) was not detected in any compost. Testosterone was detected in twelve kinds of the fifteen kinds of compost analyzed. The quantities of estrogen and androgen in the composts are as follows, El: 30580 ng/g; E2: Less than the minimum limit of detection (N.D.) -23 ng/g; E3: N.D-4 ng/g; EE2: N.D. and testosterone: N.D.-2, 100 ng/g.<BR>Estrogenic and androgenic activities were investigated for twenty-one kinds of composts using a yeast two-hybrid assay. Estrogenic activities were confirmed with thirteen kinds of composts and androgenic activities were confirmed with two kinds of composts. The estrogenic and androgenic activities measured by using human estrogen receptor <I>a</I> (hER<I>a</I>), medaka fish estrogen receptor <I>a</I> (medER<I>a</I>) and human androgen receptor (hAR) are as follows, hER<I>a</I>: 14-168 pM E2 equivalency quantity (EEq) /compost (g) ; medER<I>a</I>: 91-581 pM EEq/compost (g) and hAR: 5-7 pM 5 <I>a</I>-dihydrotestosterone equivalent quantity (AEq) /compost (g) . This paper shows that sex hormones were detected in most compost produced from the sewage sludge and solid waste of livestock. Moreover, estrogenic activities were confirmed with over half of these composts.

DOI： 10.5985/jec.16.615

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

The oxidative photodegradation behaviors of selected polychlorinated biphenyls (PCBs) [2,3,3',4'-tetraCB (BZ number: CB56), 2,3',4',5-tetra (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 (hER alpha). 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 17 beta-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.

DOI： 10.1021/es050791a

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There are growing concerns about health risks in pet animals due to the exposure to brominated compounds. This chapter describes the available information on tissue-specific accumulation and biotransformation of PBDEs and their hydroxylated and methoxylated derivatives (OH-PBDEs and MeO-PBDEs) in pet dogs and cats. Cats tend to exhibit higher tissueand blood concentrations of PBDEs. Furthermore, brominated compounds are also found at relatively high concentrations in cat brains, suggesting that they can cross through the blood–brain barrier. Thus, cats might be at a high risk from PBDEs and their derivatives. In dogs, BDE47 is the dominant congener in the bile, which suggests a species-specific excretory capacity of the liver. Regarding PBDEs metabolites, 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. The profiles and tissue distribution of PBDEs and metabolites are described for both species, and possible explanations for the differencesobserved between these pets are put forward.

DOI： 10.1007/978-3-030-30734-9_6

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有機ハロゲン化合物の一種であるポリ塩化ビフェニル（PCBs）は甲状腺ホルモン（THs）の恒常性かく乱が懸念されており、実際、ヒトやげっ歯類においてはPCBs暴露により血中THs濃度の低下が認められている。ヒトの身近な動物であるネコは餌などを介してPCBsに暴露していると懸念され、THs恒常性に何らかの悪影響をもたらすことが予想される。本研究では、ネコの甲状腺機能に対するPCBsの影響を解析するため、&lt;i&gt;in vivo&lt;/i&gt;投与試験したネコを用いて甲状腺機能への影響を解析した。血中のTHs濃度（総T4、総T3、遊離T4、遊離T3、リバースT3）を解析した結果、対照群と暴露群の間に有意な差は見られなかった。また、THsの恒常性に関与する遺伝子（甲状腺ホルモン受容体αおよびβ、脱ヨード酵素type1）の肝臓中発現量やTHs代謝に関わる酵素であるグルクロン酸抱合酵素（UGT1A1）の活性を調べたところ、対照群と暴露群の間に有意な差は見られなかった。&lt;br&gt;本実験結果では、ネコにおいてPCBs短期暴露によるTHsへの影響が認められなかったが、日本のペットネコにおけるモニタリング調査では、血中のTHs濃度とPCBs濃度との間に負の相関が見られており、有機ハロゲン化合物によるTHsかく乱が懸念されている。また、本研究試料のメタボローム解析結果では酸化ストレスの発現、抗酸化物質、電子伝達物質の生産阻害などが示唆されており、PCBsや水酸化代謝物による内分泌撹乱作用が心配される。THsの恒常性は非常に複雑な機構のもと維持されていることが知られており、負のフィードバック機構に加え、THsの活性化や代謝、排泄の調整にも多くの遺伝子やトランスポーター、酵素など様々な要因が関わっていることから、ネコは長期的かつ慢性的に化学物質に暴露されることで、甲状腺機能などへの悪影響が現れると考えられ、内分泌撹乱作用の作用機序について解析を進めることが重要である。

DOI： 10.14869/toxpt.44.1.0_P-55

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ポリ塩化ビフェニル（PCBs）の水酸化代謝物であるOH-PCBsは、肝臓内で薬物代謝酵素より生成され、その後体外へ排泄される。しかしながら、一部の水酸化代謝物は甲状腺ホルモン（TH）と類似の構造をもつため、THの恒常性を撹乱することが危惧されている。これまでに、多様な陸棲哺乳類の血中OH-PCBsを分析したところ、種間でOH-PCBsの組成に差異が認められ、中でも、ネコのOH-PCBs残留パターンは他種と大きく異なることから、本種は特異な代謝機能を有することが示唆された。しかし、ネコの異物代謝能の研究は僅かであり、化学物質暴露による毒性影響も不明な点が多い。本研究では、ネコにおけるPCBs &lt;i&gt;in vivo&lt;/i&gt;暴露試験を実施し、体内動態および代謝に関与する酵素活性や遺伝子を解析するとともに、化学物質の暴露評価に繋がる基盤的情報の収集を目的とした。&lt;br&gt;コーン油に溶解した12異性体のPCBsを腹腔内投与し、経時採血した血清中PCBsおよびOH-PCBs濃度について同条件で実施したイヌの&lt;i&gt;in vivo&lt;/i&gt;試験と比較した結果、異性体の残留パターンや体内動態にイヌとネコで種差が観察された。とくにネコでは低塩素化体の残留が顕著であった。また、代謝酵素活性および遺伝子解析の結果、PCBs暴露によりEROD、MROD、PROD活性は上昇するものの、第2相抱合酵素（UGTやSULT）活性は変化せず、PCBs暴露による抱合酵素活性への影響もみられなかった。また、&lt;i&gt;CYP1A1&lt;/i&gt;および&lt;i&gt;CYP1A2&lt;/i&gt;遺伝子の発現量の上昇も認められた。&lt;br&gt; 本研究により、ネコのPCBs吸収・代謝・排泄能はイヌと異なることが示唆され、とくに低塩素化OH-PCBsの毒性リスクは高いことが予想された。低塩素化OH-PCBsは血中でTH輸送タンパクとの競合結合や、THの硫酸抱合排泄の阻害、TH起因性遺伝子の転写抑制などが報告されており、ネコの甲状腺機能障害が懸念される。

DOI： 10.14869/toxpt.43.1.0_P-6

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

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Language：Japanese   Publisher：環境ホルモン学会(日本内分泌撹乱化学物質学会)  

J-GLOBAL

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Event date： 2023.5 - 2023.6

Presentation type：Poster presentation  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2023.5 - 2023.6

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2023.5 - 2023.6

Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Event date： 2023.5

Language：Japanese  

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Event date： 2022.2

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2022.2

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2021.9

Language：Japanese  

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Event date： 2021.6

Presentation type：Oral presentation (general)  

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Event date： 2020.9

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2020.9

Language：English   Presentation type：Poster presentation  

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Event date： 2020.9

Language：Japanese  

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Event date： 2019.12

Language：Japanese  

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Event date： 2019.6

Language：Japanese  

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Event date： 2019.6

Language：Japanese  

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Event date： 2019.6

Language：Japanese  

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Event date： 2018.12

Language：English  

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Event date： 2018.8

&lt;p&gt;[in Japanese] &lt;/p&gt;

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Event date： 2018.8

Language：Japanese  

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Event date： 2018.5

Language：Japanese  

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Event date： 2018.5

Language：Japanese  

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Event date： 2018.5

Language：Japanese  

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Event date： 2018.5

Language：Japanese  

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Event date： 2018.5

Language：Japanese  

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Event date： 2017.12

Language：Japanese  

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Event date： 2017.12

Language：Japanese  

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Event date： 2017.6

Language：Japanese  

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Event date： 2017.6

Language：Japanese  

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Event date： 2017.6

Language：Japanese  

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Event date： 2010.6

Language：Japanese  

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Event date： 2005.9

Language：Japanese  

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Event date： 2004.12

Language：Japanese  

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Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

Venue：Sapporo, Japan  

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Presentation type：Oral presentation (general)  

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Venue：Sapporo, Japan  

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Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

Venue：Matsuyama, Japan  

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Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

Venue：Matsuyama, Japan  

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Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

Venue：Giza, Egypt  

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Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

Venue：Kobe, Japan  

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Language：English   Presentation type：Poster presentation  

Venue：Sapporo, Japan  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：藤沢市  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：静岡市  

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Language：Japanese   Presentation type：Poster presentation  

Venue：つくば市  

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Language：English   Presentation type：Oral presentation (general)  

Venue：National University, Gwangju, Korea  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：松山市  

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Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：秋田市  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

Venue：Orlando, FL, USA  

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Language：English   Presentation type：Poster presentation  

Venue：Orlando, FL, USA  

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Language：English   Presentation type：Poster presentation  

Venue：Orlando, FL, USA  

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Language：English   Presentation type：Oral presentation (general)  

Venue：Kobe, Japan  

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Language：English   Presentation type：Oral presentation (general)  

Venue：Kennedy Space Center FL, USA  

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Language：English   Presentation type：Oral presentation (general)  

Venue：Orlando, FL, USA  

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Language：English   Presentation type：Poster presentation  

Venue：Orlando, FL, USA  

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Language：English   Presentation type：Oral presentation (general)  

Venue：Kobe, Japan  

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Language：English   Presentation type：Poster presentation  

Venue：Kobe, Japan  

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Language：English   Presentation type：Poster presentation  

Venue：Kobe, Japan  

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Language：English   Presentation type：Poster presentation  

Venue：Kobe, Japan  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (invited, special)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：秋田  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：秋田  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：English   Presentation type：Oral presentation (invited, special)  

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Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：札幌  

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Language：English   Presentation type：Poster presentation  

Venue：Matsuyama, Japan  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：English   Presentation type：Symposium, workshop panel (nominated)  

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Language：English   Presentation type：Symposium, workshop panel (nominated)  

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Language：English   Presentation type：Symposium, workshop panel (nominated)  

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Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Oral presentation (general)  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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