記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.chroma.2021.462686

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/etc.5212

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

A three-dimensional hydrodynamic-antibiotic model is developed to investigate the transport and dilution of sulfamethoxazole (SMX) in the Upper Gulf of Thailand (UGoT). The simulation produced a spatially averaged annual mean SMX concentration of 0.58 μgm−3, which varied slightly between seasons assuming a temporally constant river SMX loading observed in August. In contrast, the horizontal distribution of SMX concentrations strongly varied with season because of the changing residual currents. In addition, SMX is diluted to concentrations lower than 10% of those in river waters a short distance offshore of the estuaries. To better understand this behavior, we examined the relationship between salinity and SMX concentrations in the UGoT. The annual budget demonstrates that 98% of SMX in the UGoT is removed by natural decomposition. As the concentrations of fluvial pollutants in the UGoT depend on their river loading and decomposition rates, functions were derived to predict pollutant concentrations and flushing times based on the river input flux and half-life.

DOI： 10.1016/j.envpol.2021.117779

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.chemosphere.2021.130591

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This review provides focused insights into the contamination status, sources, and ecological risks associated with multiple classes of antibiotics in surface water from the East and Southeast Asia based on publications over the period 2007 to 2020. Antibiotics are ubiquitous in surface water of these countries with concentrations ranging from <1 ng/L to hundreds μg/L and median values from 10 to 100 ng/L. Wider ranges and higher maximum concentrations of certain antibiotics were found in surface water of the East Asian countries like China and South Korea than in the Southeast Asian nations. Environmental behavior and fate of antibiotics in surface water is discussed. The reviewed occurrence of antibiotics in their sources suggests that effluent from wastewater treatment plants, wastewater from aquaculture and livestock production activities, and untreated urban sewage are principal sources of antibiotics in surface water. Ecological risks associated with antibiotic residues were estimated for aquatic organisms and the prevalence of antibiotic resistance genes and antibiotic-resistant bacteria were reviewed. Such findings underline the need for synergistic efforts from scientists, engineers, policy makers, government managers, entrepreneurs, and communities to manage and reduce the burden of antibiotics and antibiotic resistance in water bodies of East and Southeast Asian countries.

DOI： 10.1016/j.scitotenv.2020.142865

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担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.chroma.2020.461586

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.scitotenv.2019.07.042

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掲載種別：研究論文（学術雑誌）  

© 2019 Elsevier B.V. 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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担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.scitotenv.2019.02.090

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Academic Press Inc.  

Triclosan (TCS), a commonly used antimicrobial compound, has recently been detected in the eggs of wild avian species. Exposure to TCS in rodents is known to interfere with thyroid hormone (TH), disrupt immune responses and cause liver disease. However, no attempt has been made to clarify the effects of TCS in avian species. The aim of this study is therefore to evaluate the toxic effects of in ovo exposure to TCS and explore the molecular mechanism by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were treated with graded concentration of TCS (0.1, 1 and 10 μg/g egg) at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At the administration of 10 μg TCS/g egg, embryo mortality increased from 20% in control to 37% accompanied with 8% attenuation in tarsus length. While liver somatic index (LSI) in TCS treatments was enhanced, statistical difference was only observed at the treatment of 0.1 μg TCS/g egg in females. The up-regulation of several crucial differentially expressed genes (DEGs) in transcriptome analysis suggested that TCS induced xenobiotic metabolism (e.g. CYP2C23a, CYP2C45 and CYP3A37 in males
CYP2C45 in females) and activated the thyroid hormone receptor (THR) - mediated downstream signaling (e.g. THRSPB and DIO2 in males
THRSPB in females). In females, TCS may further activate the lipogenesis signaling (e.g. ACSL5, ELOVL2) and repress the lipolysis signaling (e.g. ABHD5, ACAT2). A battery of enriched transcription factors in relation to these TCS-induced signaling and phenotypes were found, including activated SREBF1, PPARa, LXRa, and LXRb in males and activated GLI2 in females
COUP-TFII was predicted to be suppressed in both genders. Finally, we developed adverse outcome pathways (AOPs) that provide insights into the molecular mechanisms underlying the alteration of phenotypes.

DOI： 10.1016/j.taap.2018.03.026

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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掲載種別：研究論文（学術雑誌）   出版者・発行元：Bentham Science Publishers  

DOI： 10.2174/157341101102150223141925

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：産業と環境  

総説

CiNii Books

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：日本毒性学会  

&lt;p&gt; 近年、ペット動物に対するポリ塩化ビフェニル（PCBs）および水酸化代謝物（OH-PCBs）の曝露による甲状腺ホルモン（THs）の恒常性への影響が注目されている。本研究ではPCBs曝露がペット動物のTHs恒常性に及ぼす影響を明らかにするため、イヌ・ネコのPCBs投与試験を実施し、PCBs曝露に伴う血清中THs濃度の変化を解析した。&lt;/p&gt;&lt;p&gt; PCBs投与後から5日間、継続的に血清を採取し、THs濃度の変化を解析した結果、ネコ血清中THs濃度は、総THs、遊離型THsともに対照群と投与群の間に有意な変化は認められなかった。一方、イヌ血清中総THs濃度は投与群において、総L-サイロキシン（T4）と総3,5,3&#039;-トリヨード-L-サイロニン（T3）の減少傾向がみられ、総PCBs濃度は総T4、総T3濃度と有意な負の相関を示した（p &lt; 0.01）。一方、遊離型T4、遊離型T3濃度では、対照群と投与群の間に経時的な変化は認められなかったが、曝露後48、96時間目で有意に増加した（p &lt; 0.05）。加えて、遊離型T4濃度は総OH-PCBs濃度と正の相関を示し（p &lt; 0.01）、異性体別ではT4様構造の高塩素化OH-PCBsで同様の傾向が認められた。上記の結果および先行研究から、PCBs曝露によるイヌ血清中THsへの影響を推察した。PCBsがT4様構造のOH-PCBsへ代謝されてTHs輸送タンパクに競合結合し、結合できない遊離型T4が血中に増加することで、THsの臓器・組織への取り込み量が増加したと予測される。その結果、イヌ肝臓中のTHs濃度は増加し、PCBs曝露により肝臓中のAhR・CARが過剰に誘導されることで、UGTおよびSULTが誘導され、THsの抱合化を促進することで体外排泄量が増加し、血清中総T4、T3が減少したものと推察された。&lt;/p&gt;

J-GLOBAL

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記述言語：英語   出版者・発行元：環境ホルモン学会(日本内分泌撹乱化学物質学会)  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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