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In this study, we aimed to identify the major aryl hydrocarbon receptor (AhR) agonists in surface sediments (S1-S10, n = 10) from Kongsfjorden, Arctic Svalbard, using effect-directed analysis. High AhR-mediated potencies were observed in the mid-polar fractions and RP-HPLC subfractions (F2.6-F2.8; log K OW 5-8) in the sediments of sites S2 and S3, which are located near abandoned coal mine areas, as assessed by the H4IIE-luc bioassay. The concentrations of traditional polycyclic aromatic hydrocarbon (t-PAHs), emerging PAHs, alkyl-PAHs, and styrene oligomers ranged from 6.1 to 2100 ng g -1 dry weight (dw), 0.5-1000 ng g -1 dw, 47 to 79,000 ng g -1 dw, and 4.2-130 ng g -1 dw, respectively, with elevated levels in S2 and S3. Principal component analysis coupled with multiple linear regression suggested that t-PAHs in sediments primarily originated from coal, petroleum combustion, and coal combustion. Twenty-four target AhR agonists accounted for 3.2%-100% (mean = 47%) of the total AhR-mediated potencies in S2 and S3. Nontarget screening via GC-QTOFMS in the highly potent fractions identified 48 AhR agonist candidates through four-step selection criteria. Among these, 27 compounds were identified as coal-derived substances. VirtualToxLab in silico modeling predicted that most of the 48 tentative AhR agonist candidates could bind to AhR. Overall, our findings indicate significant contamination of the Kongsfjorden sediments by coal-derived substances, highlighting the need for further studies to assess the ecological risks associated with these contaminants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Organophosphate esters (OPEs) are emerging contaminants that serve as alternatives to regulated substances in aquatic environments. A nationwide large-scale assessment for OPEs, including point sources, remains insufficient. To address this issue, we aimed to investigate OPEs occurrence and novel OPEs via comprehensive target, suspect and non-target analysis. Among the 11 target OPEs, 10 were detected at sampling sites distributed evenly nationwide. The highest mean concentrations were measured for tris-(2-butoxyethyl) phosphate (TBOEP) and tris(2-chloroisopropyl) phosphate (TCIPP). The multivariate statistical analysis revealed that TBOEP and TCIPP are essential components for assessing total OPEs pollution. The systematic risk assessment results evaluated the overall risk contribution of TBOEP and the significant risk impact of 2-ethylhexyl diphenyl phosphate. Promising suspect and non-target analysis enabled frequent detection and identification of 6 antioxidant transformation products (TPs), as well as the tentative identification of 14 OPEs and TPs, including 3 di-OPEs. Based on sampling site classification, we confirmed that major OPEs are significantly discharged near point sources. We believe that this is the first attempt to assess the nationwide risk and potential sources of OPEs in Korean surface waters, providing insights that could support further prioritization and regulation efforts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Junho Jeon reports financial support was provided by Changwon National University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Few studies have been conducted on the occurrence and distribution of alternative plasticizers (APs) in aquatic environments. Legacy plasticizers (LPs) and APs were measured in sediments collected from four artificial lakes and a bay surrounded by high-tech industrial complexes. Bis(2-ethylhexyl) phthalate (DEHP) and bis(2-ethylhexyl) terephthalate were major plasticizers. The concentrations of LPs and APs in sediment were similar, implying rapid adoption of APs. The highest AP concentrations were observed in sediment from a lake close to semi-conductor, liquid crystal display, and automobile manufactures, suggesting a preferential shift to APs. Contamination profiles of APs differed according to industrial type. The mass inventories of plasticizers in sediment from the lakes were 25 times higher than those from the bay. Hydrophobicity was a major factor determinant of dilution factors of plasticizers in sedimentary environments. The DEHP concentrations in lake sediments exceeded threshold values, indicating potential health risks to benthic organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The routine use of chemicals in polar regions contributes to unexpected occurrence of micropollutants, with sewage discharge as a prominent pollution source. The aim of this study was to identify and quantify micropollutants in polar environments near potential point sources using non-target analysis (NTA) with liquid chromatography high-resolution mass spectrometry. Seawater samples were collected from Ny-Ålesund, Svalbard and Marian Cove, King George Island, in 2023. We tentatively identified 32 compounds with NTA, along with 105 homologous series substances. Of these, 18 substances were confirmed, and 13 were quantified using the internal standard method. Most quantified substances in the Ny-Ålesund, including caffeine, naproxen, and polyethylene glycols (PEGs), exhibited concentrations ranged from 0.9 to 770,000 ng/L. In Marian Cove, the analysis predominantly detected acetaminophen, with concentrations ranging from 13 to 35 ng/L. The findings underscore the presence and spatial distribution of emerging micropollutants resulting from wastewater discharge in polar regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Gamcheon Harbor in Busan, the largest port city in South Korea, is contaminated with persistent toxic substances, including polycyclic aromatic hydrocarbons (92 to 1700 ng g -1 dry mass (dm)) and styrene oligomers (17 to 520 ng g -1  dm). This study applied effect-directed analysis and nontarget screening (NTS) to identify aryl hydrocarbon receptor (AhR)-active substances in Gamcheon harbor sediments. Relatively great AhR-mediated potencies were found in RP-HPLC fractions, F2.7-F2.8 (mid-polar, log K OW 6-8) and F3.6-F3.7 (polar, log K OW 5-7). Target AhR agonists comprised up to 43% of total AhR-mediated potencies. NTS using GC-QTOFMS and LC-QTOFMS identified daphnoretin and isorhamnetin as significant AhR agonists, with relative potency values of 0.4 × 10 -3 and 6.5 × 10 -5 , respectively, compared to benzo[a]pyrene. The major AhR agonists in the coastal sediments of Korea appeared to be region-specific. This approach is useful for identifying and managing key toxic substances in coastal ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Diisononyl phthalate (DiNP) has been used to replace bis(2-ethylhexyl) phthalate (DEHP) and is frequently found in the environment and humans. DiNP is reported for its anti-androgenic activity; however, little is known about its effects on thyroid function and neurodevelopment. In the present study, the thyroid disruption and neurobehavioral alteration potential of DiNP and its major metabolites were assessed in a rat pituitary carcinoma cell line (GH3) and embryo-larval zebrafish (Danio rerio). In GH3 cells, exposure to DiNP and its metabolites not only increased proliferation but also induced transcriptional changes in several target genes, which were different from those observed with DEHP exposure. In larval fish, a 5-day exposure to DiNP caused significant increases in thyroid hormone levels, following a similar pattern to that reported for DEHP exposure. Following exposure to DiNP, the activity of the larval fish decreased, and neurodevelopment-related genes, such as c-fos, elavl3, and mbp, were down-regulated. These changes are generally similar to those observed for DEHP. Up-regulation of gap43 and down-regulation of elavl3 gene, which are important for both thyroid hormone production and neurodevelopment, respectively, support the potential for both thyroid and behavioral disruption of DiNP. Overall, these results emphasize the need to consider the adverse thyroid and neurodevelopmental effects in developing regulations for DEHP-replacing phthalates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Di(2-ethylhexyl) terephthalate (DEHTP) is an alternative plasticizer widely used in numerous consumer products, replacing di(2-ethylhexyl) phthalate (DEHP). Hence, DEHTP has been frequently detected in the environment and humans. As a structural isomer and functional analog of DEHP, DEHTP is a suspected endocrine disruptor. Here, we evaluated thyroid-disrupting effects of DEHTP using embryo-larval and adult male zebrafish. We also investigated its sex hormone disruption potential in the adult zebrafish. After 5- and 7-days of exposure to DEHTP, significant increases in whole-body thyroid hormonal levels were observed in the larval fish. Down-regulation of several thyroid-regulating genes, including trh, tshβ, nis, and dio2, was observed, but only after 5-day exposure. Following a 21-day exposure, the adult male zebrafish exhibited a significant decrease in total triiodothyronine and an increase in thyroid-stimulating hormones. Potential changes in the deiodination of thyroid hormones, supported by the up-regulation of two deiodinases, dio1 and dio3a, along with the down-regulation of dio2, could explain the thyroid hormone changes in the adult zebrafish. Moreover, significant trends of decrease in estradiol and 11-ketotestosterone, along with increase of testosterone (T), were observed in the adult zebrafish. Up-regulation of several steroidogenic genes may explain elevated T, while exact mechanisms of action warrant further investigation. Our results demonstrate that DEHTP can cause disruptions of thyroid and sex hormones at different life stages in zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Legacy and emerging per- and polyfluoroalkyl substances (PFASs) were measured in livers of finless porpoises (Neophocaena asiaeorientalis; n = 167) collected in Korean waters from 2002 to 2015 to investigate their occurrence, bioaccumulation feature, temporal trends, and ecotoxicological implications. Perfulorooctane sulfonate (PFOS), perfluoroundecanoate (PFUnDA), and perfluorotridecanoate (PFTrDA) were the predominant PFASs found in the porpoises. The concentration of 6:2 chlorinated polyfluoroalkyl ether sulfonate (F-53B), an alternative to PFOS, was comparable to that of PFTrDA. Perfluorooctane sulfonamide (FOSA), a precursor of PFOS, was also detected in all the porpoises examined. All PFASs, including F-53B, accumulated to higher concentrations in immature porpoises compared with mature specimens, implying substantial maternal transfer and limited metabolizing capacity for PFASs. A significant correlation was observed between PFOS and F-53B concentrations, indicating similar bioaccumulation processes. Based on prenatal exposure and toxicity, F-53B is an emerging contaminant in marine ecosystems. Significantly increasing trends were observed in the concentrations of sulfonates, carboxylates, and F-53B between 2002/2003 and 2010, whereas the FOSA concentration significantly decreased. During 2010-2015, decreasing trends were observed in the concentrations of FOSA and sulfonates, whereas concentrations of carboxylate and F-53B increased without statistical significance, likely due to a gap for the implementation of regulatory actions between sulfonates and carboxylates. Although PFOS and PFOA were found to pose little health risk to porpoises, the combined toxicological effects of other contaminants should be considered to protect populations and to mitigate PFAS contamination in marine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lead (Pb) and mercury (Hg) are neurodevelopmental toxicants that pose risks to cognitive and behavioral health. Given early childhood's vulnerability to these metals, understanding their sources and pathways of exposure during infancy is crucial for public health. During the weaning process, infants may be exposed to metals through the baby food they consume. We aimed to assess metal exposure through homemade weaning foods by analyzing 288 samples consumed by 157 Korean infants aged 6-, 9-, 12-, 15-, and 24-27 months. Pb was detected in 65 % of samples, with levels reaching up to 169 ng/g. Notably, 58 % exceeded the Maximum Level (ML) of 10 ng/g, with a median concentration of 14.7 ng/g fresh weight. Total Hg was found in 88 % of samples, with a median concentration of 4.56 ng/g fresh weight. Estimated median daily intakes of Pb and Hg were 0.29 and 0.09 μg/kg/d, respectively. Considering a benchmark dose for Pb (0.5 μg/kg/d by EFSA), 94 % (the margin of exposure <10) of all age groups was estimated to have a potential health concern associated with homemade baby food consumption. For Hg, only 6 % exceeded a hazard quotients of 1 compared to a provisional tolerable weekly intake for Hg (4 μg/kg/week by WHO). This study marks the first direct assessment of daily Pb and Hg intake through homemade baby food among Korean infants. Our findings underscore the urgent need for heightened awareness regarding metal exposure through homemade baby food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Siloxanes have been commonly used as additives in a variety of industrial and consumer products. Media and government investigations have revealed that defoamers containing siloxanes are used in the effluent of thermal power plants in Korea. However, investigations of the source impact of siloxane contamination from the discharge of thermal power plants into coastal environments are scarce. In this study, sediment and invertebrates were collected around a thermal power plant to assess source impact, seasonal variation, and a potential for bioaccumulation. Although siloxanes were detectable in sediment and invertebrates, the spatial distribution and composition (which differed between the siloxanes found in sediment and invertebrates and those in defoamer used in the plant) suggest they were likely transported by long-distance migration as well as the discharge of thermal power plant. Seasonal differences might affect sedimentary contamination and the bioaccumulation potential of siloxanes. Specifically, octamethylcyclotetrasiloxane (D4) may have limited adsorption capacity and potential for long-distance migration, as its contribution in sediment far from the coastline was greater than that of decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6). However, higher D5 accumulation in invertebrates, and D5 has a potential bioaccumulation. A molecular docking analysis showed that the binding affinity between D5 and the cytochrome enzyme in invertebrates was weaker than that with other siloxanes, which could lead to higher D5 accumulation in invertebrates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study introduces a novel concept approach for a read-across assessment, considering species sensitivity differences among phosphate chemicals within structurally similar compound groups. Twenty-five organic chemicals, with a log Kow of 5 or less, were categorized into three functional groups based on acetylcholinesterase (AChE) inhibition as a specific mode of action (MOA). The short-term aquatic toxicity data (LC 50 ) for fish, crustaceans, and insects were collected from the U.S. EPA Ecotoxicology (ECOTOX) Knowledgebase. A geometric mean calculation method was applied for multiple toxic endpoints. Performance metrics for the new read-across concept, including correlation coefficient, bias, precision, and accuracy, were calculated. Overall, a slightly higher overestimation (49.2%) than underestimation (48.4%) in toxicity predictions was observed in two case studies. In Case study I, a strong positive correlation ( r = 0.93) between the predicted and known toxicity values of target chemicals was observed, while in Case study II, with limited information on species and their ecotoxicity, showed a moderate correlation ( r = 0.75). Overall, the bias and precision for Case study I were 0.32 ± 0.01, while Case study II showed 0.65 ± 0.06; however, the relative bias (%) increased from 37.65% (Case study I) to 91.94% (Case study II). Bland-Altman plots highlight the mean differences of 1.33 (Case study I) and 1.24 (Case study II), respectively. The new read-across concept, focusing on AChE inhibition and structural similarity, demonstrated good reliability, applicability, and accuracy with minimal bias. Future studies are needed to evaluate various types of chemical substances, diverse modes of action, functional groups, toxic endpoints, and test species to ensure overall comprehensiveness and robustness in toxicity predictions.

Siloxanes, widely used in various consumer and industrial products, are emerging concerns of contaminants. Despite this, limited studies have been conducted on contamination and time trends on siloxanes in coastal environments. In the present study, four cyclic and 15 linear siloxanes were measured in sediments collected from an artificial saltwater lake in Korea during 2001-2016 to investigate contamination, time trends, and ecotoxicological concerns. Cyclic siloxanes were detected in all sediment samples, whereas linear siloxanes were not frequently detected. The highest siloxane concentrations were observed in creeks passing through various industrial complexes, indicating that industrial activities predominantly contributed to siloxane contamination in coastal environments. Decamethylcyclopentasiloxane (D5) and dodecylcyclohexasiloxane (D6) were predominant siloxanes in sediments over the last two decades. Siloxane concentrations significantly increased in creek sediments from 2008 to 2016, whereas those in inshore and offshore regions significantly decreased due to a strong dilution effect by the operation of tidal power plant. This suggests that consumption patterns and coastal development activities are crucial factors determining the contamination and time trends in the sedimentary siloxanes. The sedimentary concentrations of octamethylcyclotetrasiloxane (D4) and D5 exceeded several thresholds, raising the potentials for ecological risks to aquatic organisms., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Novel and emerging per- and polyfluoroalkyl substances (PFAS) are a key issue of concern in global environmental studies. In this study, air, sediment, and wastewater samples were collected from areas in and/or surrounded by fluorochemical-related industrial facilities to characterize the contamination profiles of neutral and novel PFAS (n-PFAS) using a gas chromatograph-based target and non-target analyses. Fluorotelomer alcohols were predominant in the samples, accounting for 80 % of the n-PFAS, followed by fluorotelomer acrylates. Air samples collected proximate to the durable water repellent (DWR) facility had the highest concentration of n-PFAS, which was approximately two orders of magnitude higher than those found in others. Non-target analysis identified fluorotelomer iodides and fluorotelomer methacrylate in multiple matrices near DWR facilities, indicating significant contamination of n-PFAS. Levels of both C6- and C8-based PFAS reflected a shift in usage patterns from C8- to C6-based fluorochemicals. Matrix-dependent profiles of n-PFAS revealed that shorter-chain (e.g., C6) and longer-chain (>C8) PFAS were predominant in air and sediment, respectively, implying that air and sediment are mobile and secondary sources of PFAS. Untreated and treated industrial wastewater also contained n-PFAS and their transformation products. The findings shed light on our understanding of the multi-matrix distribution and transport of PFAS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Siloxanes and synthetic musk compounds (SMCs) have been widely used as additives in household and personal care products. Humans are easily exposed to siloxanes and SMCs originating from these products through ingestion and dermal absorption of indoor dust. In the present study, indoor dust samples were analyzed for 19 siloxanes (cyclic and linear) and 12 SMCs (polycyclic, macrocyclic, and nitro musks) to assess their occurrence, time trends over time, source, and health risks. A total of 18 siloxanes and 10 SMCs were detected in all indoor dust samples obtained from 2011⎯2021, indicating widespread and long-term contamination. Higher detection frequencies and concentrations were associated with siloxanes and SMCs with higher use and strong resistance against degradation processes. Indoor dust samples were dominated by linear siloxanes (L11-L13), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran (HHCB), musk ketone (MK), and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN). The frequent use of household and personal care products is likely an important source of siloxane and SMC contamination in indoor environments. The concentrations of siloxanes and SMCs in indoor dust increased from 2011 to 2021, particularly, those of linear siloxanes, reflecting the impact of regulatory actions addressing cyclic siloxanes. The profiles of siloxanes remained stable throughout the study period, whereas those of SMCs shifted from nitro to polycyclic musks. The estimated daily intakes (EDIs) of siloxanes and SMCs arising from ingestion were greater than from dermal absorption of indoor dust. The EDIs of siloxanes and SMCs associated with indoor dust indicated that children are exposed to these pollutants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Major aryl hydrocarbon receptor (AhR) agonists were identified in extracts of blubber, liver, and muscle from six long-beaked common dolphins ( Delphinus capensis ) and one fin whale ( Balaenoptera physalus ) collected from Korean coastal waters using effect-directed analysis. Results of the H4IIE- luc bioassay indicated that the polar fractions of blubber and liver extracts from the fin whale exhibited relatively high AhR-mediated potencies. Based on full-scan screening with high-resolution mass spectrometry, 37 AhR agonist candidates, spanning four use categories: pharmaceuticals, pesticides, cosmetics, and natural products, were selected. Among these, five polar AhR agonists were newly identified through toxicological confirmation. Concentrations of polar AhR agonists in cetaceans were tissue-specific, with extracts of blubber and liver containing greater concentrations than muscle extracts. Polar AhR agonists with great log K OA values (>5) were found to biomagnify in the marine food chain potentially. Polar AhR agonists contributed 8.9% of the observed AhR-mediated potencies in blubber and 49% in liver. Rutaecarpine and alantolactone contributed significantly to the total AhR-mediated potencies of blubber, whereas hydrocortisone was a major AhR contributor in the liver of the fin whale. This study is the first to identify the tissue-specific accumulation of polar AhR agonists in blubber and liver extracts of cetaceans.

Although firefighters are at an increased risk of occupational exposure to chemicals, such as flame retardants, research on the exposure of Korean firefighters to organophosphate esters (OPEs)-a group of emerging flame retardants-remains limited. Therefore, in the present study, OPE metabolite concentrations in the urine samples of 149 former and current Korean firefighters were measured. Based on the data obtained, the estimated daily intakes (EDIs) of OPEs were calculated. Subsequently, the association between the urinary concentrations of OPE metabolites and the potential determinants of OPE exposure and health outcomes (e.g., obesity and serum lipids) was investigated. We found that bis(1-chloro-2-propyl) phosphate (BCIPP) and bis(2-chloroethyl) phosphate (BCEP) were the most prevalent urinary OPE metabolites, with median concentrations of 2.33 and 1.80 ng/mL, respectively; these concentrations were higher than those reported previously in other countries, such as the USA and China. Moreover, their parent compounds-tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(2-chloroethyl) phosphate (TCEP)-exhibited EDIs of 126 and 94.8 ng/kg bw/day, respectively. Unlike the high detection rate of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) in other populations, its detection rate in this study was low (6.7%), suggesting regional differences in the exposure pattern of OPEs among countries. Furthermore, occupational characteristics, such as recent participation in firefighting activity, were identified as determinants of the urinary concentrations of OPE metabolites. Total OPE metabolites were inversely associated with body mass index and positively associated with high-density lipoprotein cholesterol. Overall, our findings demonstrate that Korean firefighters are highly exposed to several occupation-related OPEs. Further prospective studies will help elucidate the potential health implications of occupational exposure to OPEs among firefighters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Few studies have been conducted on spatial and temporal trends in polychlorinated naphthalenes (PCNs) in coastal environments. Here, we describe 18 PCN congeners found in surface and dated sediment samples collected from highly industrialized bays of Korea. Measurable levels of PCN congeners were detected in all sediment samples, suggesting concurrent and historical contamination. The highest PCN concentrations were observed in sediment from rivers, streams, and the inner portions of the bays, which are surrounded by industrial complexes and commercial harbors. CNs 73, 66/67, and 52 were dominant in surface and dated sediment samples. Congener patterns and diagnostic ratios revealed that PCN contamination is originated from combustion processes and the use of polychlorinated biphenyl (PCB) technical mixtures. PCN concentrations in dated sediment increased from the 1980s to the mid-2000s and then decreased to 2015. Although the toxic equivalent (TEQ) levels of PCNs in our study did not exceed sediment quality guidelines proposed by international authorities, the cumulative risks from the TEQ concentrations of polychlorinated dibenzo-p-dioxins, furans, PCBs, and PCNs can be expected for benthic organisms., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Exposure to endocrine-disrupting chemicals (EDCs) can promote infant neurodevelopmental impairment and maternal postpartum depression (PPD). However, the associations between lactation exposure to EDCs, maternal PPD, and infant neurodevelopment are unclear. Hence, we investigated these relationships in infants aged 36-42 months. We recruited 221 Korean mothers and analyzed 29 EDCs. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess maternal PPD. Bayley scales of infant development; the Swanson, Nolan, and Pelham rating scale (SNAP); and the Child Behavior Checklist (CBCL) were used to assess neurodevelopment in infants exposed to the top 30% of EDC over three years. Multiple regression analyses were adjusted for maternal age, pre-pregnancy body mass index, education, income, employment, residence, and infant age and sex. The rates of infants with clinically abnormal diagnoses on neurologic developmental tests (Balyey, SNAP, and CBCL scales) ranged from 7.7 to 38.5% in this study, with the motor and hyperactivity/impulsivity areas scoring the highest among 65 boys and girls. Mono-2-ethylhexyl phthalate (MEHP) and mono-isononyl phthalate (MiNP) levels in breast milk significantly correlated with infant inattention and hyperactivity. Perfluorononanoic acid (PFNA) and perfluorooctyl sulfonate (PFOS) levels correlated significantly with motor development of BSID-III and total CBCL score which mean infant might have lower developmental status. EDC concentrations in breast milk were not associated with maternal PPD. Overall, lactational exposure to EDCs during the postpartum period can exert a negative effect on maternal PPD and infant neurodevelopment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Synthetic musk compounds (SMCs) have been extensively used in numerous consumer products, such as perfumes, cosmetics, soap, and fabric softener. Due to their bioaccumulative nature, these compounds have often been detected in the aquatic ecosystem. However, their effects on endocrine and behavioral effects in freshwater fish have rarely been investigated. In the present study, thyroid disruption and neurobehavioral toxicity of SMCs were investigated using embryo-larval zebrafish (Danio rerio). Three frequently used SMCs, i.e., musk ketone (MK), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta [g]- benzopyran (HHCB), and 6-acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN), were chosen. Experimental concentrations for HHCB and AHTN were selected to include the maximum levels reported in the ambient water. The 5-day exposure to either MK or HHCB led to significant decrease of T4 concentration in the larval fish at the levels as low as 0.13 μg/L, even though compensatory transcriptional changes, e.g., up-regulation of hypothalamic crhβ gene and/or down-regulation of ugt1ab gene, were taken place. In contrast, AHTN exposure resulted in up-regulation of crhβ, nis, ugt1ab, and dio2 genes but did not alter T4 level, suggesting its lesser thyroid disrupting potential. All tested SMCs caused hypoactivity of the larval fish. Several genes related to neurogenesis or development, e.g., mbp and syn2a, were down-regulated, but the patterns of transcriptional changes were different among the tested SMCs. The present observations demonstrate that MK and HHCB can decrease T4 levels and cause hypoactivity of the larval zebrafish. It requires attention that HHCB and AHTN could influence thyroid hormone or behavior of the larval fish even at the levels close to those observed in the ambient environment. Further studies on potential ecological consequences of these SMCs in freshwater environment are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The concentrations and isotopic compositions of carbon (C), copper (Cu), zinc (Zn), and lead (Pb) in coastal sediments were analyzed to identify potential pollution sources. High concentrations of total organic carbon (TOC) and metals were found close to cities and industrial areas. The isotopic compositions of C, Cu, Zn, and Pb tended to decrease as their concentrations increased. Bi-plots between δ 65 Cu and δ 66 Zn showed that the isotopic compositions in most coastal sediments, except sediments around a smelter, were similar to the isotopic compositions of road dust in urban and industrial areas of Korea. Our results suggest that heavy metal pollution in coastal sediments is greatly influenced by the pollution source, such that most metals originate from traffic and industrial activities in the urban environment. This analysis of multiple isotopes provides insights concerning the transport mechanisms and clarifies potential sources of metal contamination in coastal environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Few studies have investigated the relationship between asthma and sarcopenia. We aimed to examine the relationship between asthma and sarcopenia in a community-dwelling geriatric population, especially regarding lung function and asthma control., Methods: A cross-sectional dataset from the Korean National Health and Nutrition Examination Survey 2008-2011 was utilized. Data regarding asthma history, age at asthma onset, recent asthma exacerbations, and hospitalization for asthma exacerbations were obtained using structured questionnaires. Appendicular skeletal muscle was calculated as the sum of the skeletal muscle mass, and physical activity was assessed using the International Physical Activity Questionnaire., Results: Asthma presented an estimated incidence of 6.17 ± 0.37% in the elderly. Groups were divided and analyzed according to asthma, muscle mass, and physical activity. Sarcopenia was associated with aging, male sex, smoking history, low body mass index (BMI), and reduced lung function with or without asthma. Sarcopenic asthma had a younger onset and reduced physical activity than non-sarcopenic asthma. Obstructive patterns were more frequent in asthmatics exhibiting low or moderate physical activity levels than in those with high activity, but asthma control was not associated with sarcopenia and physical activity. Multivariate logistic regression analyses showed that compared with control, sarcopenic asthma was associated with FEV1 < 60%, and airway obstruction, and with aging, male, and lower BMI, compared with non-sarcopenic asthma., Conclusions: Our findings suggest that decreased muscle mass and physical activity levels contribute to reduced lung function in elderly asthmatics. Furthermore, sarcopenic asthma was associated with aging, low BMI, and reduced lung function in the elderly.

The aim of study was to optimize an QuEChERS extraction procedure for simultaneous determination of organic pollutants in aquaculture products. The QuEChERS extracts were measured using LC-HRMS. The target contaminants include 32 pesticides and 20 pharmaceuticals which have not been regulated for the products in Korea. The method was validated according to CODEX guideline (CAC/GL 71-2009). LOD and LOQ for all analytes ranged from 0.1 to 2 μg/kg and from 0.5 to 5 μg/kg, respectively. Intra-day (n = 5) and inter-day (n = 9) accuracy and precision were evaluated with the guideline. The validated method was applied to aquaculture products (n = 303). As a result, 14 pesticides and 8 pharmaceuticals were quantified. Fluxapyroxad, a fungicide frequently detected in domestic surface waters, was found with relatively higher concentration in 17 out of 23 species. It proves that a hydrophobic inland contaminant can be accumulated in the aquaculture products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Several studies have been conducted among South Korean to investigate effects of high blood mercury (Hg) levels. In this study fetal body burden of Hg in 344 pregnant women were estimated using a physiologically-based pharmacokinetic model (PBPK) and its associative effects on the growth of infants were analyzed. The association between cord blood Hg and growth variables at birth was analyzed based on parameters such as the sex of the newborn, living area, maternal age group, gestation day, maternal body mass index . We investigated the effects of Hg on infant growth through follow-ups, using a non-linear mixed model. The mean Hg levels in maternal and cord blood were 4.47 μg/L and 7.35 μg/L, respectively. Among the subjects, the corresponding fetal body burden for Methylmercury ranged between 26.3-86.9 mg. Cord blood Hg levels positively correlated with length at birth. Furthermore, the high cord blood group showed greater growth rates compared to the low cord blood group. Therefore, we suggest that pregnant women should make efforts to mitigate exposures to Hg, specifically from diet. Further research is suggested to investigate the relationship between the follow-up growth of the infants and Hg levels, considering fish consumption, diet information, and other environmental pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Many studies have reported that neonates and infants are exposed to several per- and polyfluoroalkyl substances (PFASs) via breastfeeding; however, these studies have had small sample sizes. This study aimed to determine the concentrations and time-course trend of PFASs in breast milk and identify influencing factors governing PFAS concentrations. Between July and September (2018), 207 low-risk primiparous women were recruited from a lactation counseling clinic in Korea and their breast milk samples were tested for 14 PFASs, including four perfluoroalkyl sulfonic acids. A questionnaire survey, comprising 84 questions covering the women's demographic, obstetrical, dietary, lifestyle, behavioral, and neonatal information, was conducted to investigate associations. Twelve of the 14 PFASs were detectable in breast milk samples. Perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorodecanoic acid were detected in 100% of the samples, followed by perfluorohexanesulfonic acid (detection rate: 87%), perfluorononanoic acid (87%), and perfluorohexanoic acid (73%); the median concentrations were 0.05, 0.10, 0.031, 0.007, and 0.033 ng/mL, respectively. The PFAS concentrations in breast milk measured in our study were higher than those reported in other studies or countries. In 12 years, from 2007 to 18, the mean concentration of PFOA in breast milk increased by approximately three times (278%). The major factors associated with PFAS concentrations in the bivariate association analysis were body mass index; living area (non-metropolitan); neonatal age; and frequency of fish, ice cream, and canned food consumption. In the multiple regression model, fish consumption significantly influenced the PFOS concentrations in breast milk (β = 0.88, p = 0.033). Frequently, fish consumption has been analyzed as the main dietary factor related to PFOS concentration. Our findings suggest the need for a comprehensive cohort study on PFAS exposure and its association with infant health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Contamination of coastal environments by siloxanes is of growing concern. Sediment and bivalves were collected from 50 locations along the Korean coast to assess the geographical distribution, sources, and bioaccumulation potential of siloxanes. Cyclic and linear siloxanes were detectable in all sediment and bivalve samples. The highest siloxane concentrations were detected in sediment (656 ng/g dw) and bivalves (3273 ng/g dw) from highly industrialized bays and harbor-zones, suggesting that industrial and shipping activities are major sources of siloxanes in coastal environment. The geographical distribution of siloxanes was similar in sediment and bivalves. Sedimentary siloxanes were dominated by cyclic siloxanes, while linear siloxanes were predominant in bivalves. Bioaccumulation of linear siloxanes in bivalves originated mainly from the sedimentary environment. Mean biota-sediment accumulation factors (BSAFs) of seven siloxanes ranged from 1.26 to 6.03, indicating potential for bioaccumulation. This is the first report on the nationwide survey on siloxanes in Korean coastal waters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Personal care products (PCPs) are considered as a major source of paraben exposure; however, the dietary contribution is not well known. We compared the urinary levels of methyl-, ethyl-, and propyl-paraben (MeP, EtP, and PrP), and investigated their associations with fasting status and contacts with other potential exposure sources among Korea and the US adult women. A group of fasting, non-pregnant adult women (n = 469) was recruited from Seoul, Ansan/Incheon, and Jeju, Korea in 2015-2016, and their urine was measured for parabens. Non-fasting Korean women of matching age (25-45 years) were chosen from the Korean National Environmental Health Survey (KoNEHS) Cycle 3 (n = 579). For the US women, both fasting (n = 154) and non-fasting (n = 201) females were chosen from the NHANES 2015-2016 participants. In fasting Korean women, the urinary MeP, EtP, and PrP concentrations (median) were measured at 47.30, 17.90, and 2.30 ng/mL, respectively. Urinary EtP and PrP levels in fasting Korean women were significantly lower than those in non-fasting women (EtP and PrP median of 26.40 and 3.57 ng/mL). On average, the difference in urinary EtP levels by fasting status was greater among the highly exposed groups. In the US population, EtP levels were significantly lower (median ranged 1.55-1.80 ng/mL depending on fasting status), but MeP levels were higher (67.90-84.35 ng/mL) than those of the Korean population. When only fasting women were considered, the median EtP levels of Korean women were 11.5-fold greater than those of US women, suggesting that the non-dietary contributions of EtP exposure could not be ignored among Korean women. Regardless of fasting status, MeP and PrP were significantly correlated, and their urinary levels in fasting Korean women were correlated with the use of several personal care products. The major dietary and non-dietary sources that may explain EtP exposure in Korean women warrant further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Novel aryl hydrocarbon receptor (AhR) agonists were identified in coastal sediments in the Yellow and Bohai Seas by use of a combination of effect-directed analysis (EDA) and in silico prediction. A total of 125 sediments were screened for AhR-mediated potencies using H4IIE-luc bioassay. Great potencies were observed in organic extracts, mid-polar fraction (F2), and subfractions of F2 (F2.6-F2.9) of sediments collected from Nantong, Qinhuangdao, and Yancheng. Less than 15% AhR potencies could be explained by detected dioxin-like PAHs. Full-scan screening analysis was conducted for the more potent fractions using GC-QTOFMS to investigate the presence of unmonitored AhR agonists. A five-step prioritization strategy was applied; 92 candidate compounds satisfied all criteria. Among these chemicals, thirteen were evaluated for AhR efficacy. Six compounds; benz[b]anthracene, 6-methylchrysene, 2-methylbenz[a]anthracene, 1-methylbenz[a]anthracene, 1,12-dimethylbenzo[c]phenanthrene, and indeno[1,2,3-cd]fluoranthene, exhibited significant AhR-mediated efficacies. 1,12-dimethylbenzo[c]phenanthrene and indeno[1,2,3-cd]fluoranthene were identified as novel AhR agonists. Potency balance analysis showed that the six newly identified AhR agonists explained 0.4-100% of the total AhR-mediated potencies determined. Overall, combining EDA and in silico prediction applied in this study demonstrated the benefits of assessing the potential toxic effects of previously unidentified AhR agonists in sediments from the coasts of China and Korea., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Routinely collected data (RCD) from electronic health records (EHR) are useful for studying disease epidemiology in the real world. We examined cough presentation and cough-related healthcare utilization using an academic institutional EHR database in Korea., Methods: In this retrospective cohort study, patients with subacute (3-8 weeks) or chronic cough (> 8 weeks in duration) referred to allergy and asthma clinics were studied. Cases were identified using the search term "cough" or "coughing," which is the chief complaint, in the data fields. Structured data, including demographics, medical history, symptoms, and diagnostic tests, were analyzed. Healthcare utilization was assessed for drug prescriptions, additional tests, or outpatient visits for 1 year., Results: Cough was the chief complaint in 13,223 cases (46.7%) among 28,312 new referrals for 8 years. A total of 3810 subacute and 7150 chronic cough patients were analyzed. The common demographic profile was middle-aged woman (mean age 52.1 years), reported in 63% of the cases. Cough was frequently accompanied by anterior nasal (about 50%), lower airway (30%), or acid reflux disease symptoms (20%), and by test abnormalities in chest X-rays (14%), spirometry (23%), or T2 inflammation markers (40%). Chronic cough patients frequently required additional tests (chest CT scan: 24%), drug prescriptions (codeine: 21.5% and oral steroids: 9.9%), and long-term healthcare utilization (16.0%) for 1 year., Conclusions: Cough is a common chief complaint at allergy and asthma clinics, but the clinical presentation may be heterogeneous. Further studies are needed to understand long-term outcomes and reduce the disease burden., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Settled house dust (SHD) is a reservoir for various contaminants, including endocrine-disrupting chemicals (EDCs), trace metals, and house dust mite allergens. This study aimed to characterize various chemical and biological contaminants in SHD and identify determinants governing the indoor contaminants. In total, 106 SHD samples were collected from 106 houses in Seoul and Gyeonggi Province, Korea, in 2021. Bedding dust samples were collected from 30 of these 106 houses. All participants completed a questionnaire comprised of housing and lifestyle-related factors. The samples were analyzed for 18 organophosphate flame retardants (OPFRs), 16 phthalates, five alternative plasticizers (APs), seven trace metals, and two house dust mite allergens (Dermatophagoides farinae type 1 [Der f1] and Dermatophagoides pteronyssinus type 1 [Der p1]). A multiple regression analysis was conducted to identify the determinants governing the concentrations and profiles of various contaminants. OPFRs, phthalates, APs, and trace metals were detected in all SHD samples, indicating ubiquitous contamination in indoor environments. Among the three EDC groups, APs were detected at the highest concentrations (geometric mean [GM] (geometric standard deviation, [GSD]): 1452 (1.6) μg/g in total), followed by phthalates (GM (GSD): 676 (1.4) μg/g in total) and OPFRs (GM (GSD): 10 (1.4) μg/g in total). Der f1 was detected in all bedding dust samples with significantly higher levels than Der p1 (GM (GSD): 0.1 (1.8) μg/g vs. 1.4 × 10 -3 (2.3) μg/g). The concentrations of OPFRs, plasticizers, and trace metals in SHD were significantly associated with the type and number of electronic appliances and combustion activities. Der f1 was significantly associated with the number of occupants and water penetration. Ventilation, vacuum cleaning, and wet cleaning or dry mopping significantly reduced the levels of most contaminants in SHD. As residents are persistently exposed to a wide array of pollutants, comprehensive and adequate measures are required to prevent potential exposures., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells., Methods: Serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults. The OCRs of platelets and peripheral blood mononuclear cells (PBMCs) were assessed in 20 mL of fresh blood using a Seahorse XF analyzer. Additionally, the in vitro effects of Arochlor-1254, β-hexachlorocyclohexane, and p,p´-dichlorodiphenyltrichloroethane at concentrations of 0.1 pM to 100 nM were evaluated in human platelets, human PBMCs, and Jurkat T-cells., Results: The association between serum POP concentrations and OCR differed depending on the cell type. As serum OCP concentrations increased, basal platelet OCR levels decreased significantly; according to the OCP quintiles of summary measure, they were 8.6, 9.6, 8.2, 8.0, and 7.1 pmol/min/μg (P trend=0.005). Notably, the basal PBMC OCR levels decreased remarkably as the serum PCB concentration increased. PBMC OCR levels were 46.5, 34.3, 29.1, 16.5, and 13.1 pmol/min/μg according to the PCB quintiles of summary measure (P trend <0.001), and this inverse association was consistently observed in all subgroups stratified by age, sex, obesity, type 2 diabetes mellitus, and hypertension, respectively. In vitro experimental studies have also demonstrated that chronic exposure to low-dose POPs could decrease OCR levels., Conclusion: The findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.

Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies., (Copyright © 2022. Published by Elsevier Inc.)

Legacy and alternative halogenated flame retardants (HFRs), such as polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), and dechlorane plus (DP), were measured in dated sediments from a highly industrialized lake in Korea. All HFRs were detected in almost all of the sediment depth layers for more than 70 years, indicating a history of long-term contamination. Similar historical trends in PBDEs, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), and DP were observed in dated sediments, whereas decabromodiphenylethane (DBDPE), and 2-ethylhexyl-2,3,4,5-octabromo-1,3,3-trimethyl-1-phenylindane (OBIND) concentrations sharply increased since the 1990s. Moreover, the concentration ratios of DBDPE/BDE 209 increased from the early 1990s to the present. Our findings suggest that DBDPE and OBIND have been used as HFR alternatives. The historical record of the concentrations and profiles of legacy and alternative HFRs corresponded with industrial activities, consumption of FRs, and coastal development activities. Inventories of legacy and alternative HFRs were similar to those reported for highly industrialized regions around the globe., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The effects of asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap (ACO) on coronavirus disease 2019 (COVID-19) remain unclear., Objective: We aimed to investigate the effects of chronic obstructive airway diseases such as asthma, COPD, and ACO on COVID-19., Methods: In total, 5625 hospitalized patients with COVID-19 were divided into asthma, COPD, ACO, and control groups. A multivariate logistic regression analysis was performed to identify factors affecting the COVID-19 mortality rate. To find out whether chronic obstructive airway diseases such as asthma, COPD, and ACO affect COVID-19 mortality, 1:4 matching was performed, except for the ACO group alone due to a small number of patients., Results: The mortality rates of asthma, COPD, and ACO groups were about 2.3, 4.8, and 5.5 times higher than that of the control group, respectively. Although not statistically significant, the survival probability tended to decrease (asthma, COPD, and combined groups of asthma and ACO, hazard ratio [HR]: 1.84, 1.31, and 1.89, respectively). The survival probability of the combined groups of COPD, ACO, and asthma and the combined groups of COPD and ACO was significantly lower than that of the matched control group (HR: 3.00 and 1.99, respectively)., Conclusion: Compared to patients with COVID-19 without chronic obstructive airway disease, patients with these comorbidities are more likely to require oxygen and mechanical ventilators and have a higher mortality rate, which can be considered when classifying and monitoring patients in the era of COVID-19. Therefore, further studies are needed to evaluate the effect of chronic obstructive airway disease, especially ACO, on COVID-19 mortality., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Prenatal exposure to heavy metals is known to be associated with adverse birth outcomes and oxidative stress biomarkers. In this study, we examined whether maternal free cortisol or 8-Hydroxy-2-Deoxyguanosine (8-OHdG) could mediate associations between maternal heavy metal exposure and birth outcomes. A total of 182 healthy pregnant women were recruited. Heavy metals (including Pb, Hg, and Cd), free-cortisol, and 8-OHdG were analyzed in urine at delivery. Birth outcomes including birth weight, length, Ponderal index, and head circumference were measured. To examine associations of maternal urinary heavy metals with biomarkers and birth outcomes, generalized linear models were employed. Birth length was positively associated with Pb (β = 0.78, 95% CI: 0.09−1.46) and Hg (β = 0.84, 95% CI: 0.23−1.45) (both p < 0.05). The Ponderal index, a measure of a newborn’s leanness, was negatively associated with maternal urinary Pb (β = −0.23, 95% CI: −0.46−−0.07) and Hg (β = −0.26, 95% CI: −0.44−−0.08) (both p < 0.05). No association between maternal Cd and birth outcomes was observed. Most heavy metals showed positive associations with free cortisol and 8-OHdG. Free cortisol was identified as a mediator underlying the observed relationship between Hg and birth length or Ponderal index. This study observed adverse birth outcomes from maternal exposures to Pb and Hg. Increased free cortisol related to Hg exposure was suggested as a possible causal pathway from Hg exposure to birth outcomes such as the Ponderal index.

Background: Leukotriene receptor antagonists are recommended to treat asthma and allergic rhinitis. Although they had been used for a long time, recent studies have reported neuropsychiatric adverse drug reactions are associated with montelukast., Objective: This study analyzed the adverse drug reactions of montelukast and pranlukast, which are the two most frequently prescribed leukotriene receptor antagonists, respectively in Korea., Methods: This study retrospectively reviewed ADRs of 5,426 montelukast and 1,146 pranlukast reported in the Korea Adverse Event Reporting System between January 2014 and December 2018., Results: When both drugs are classified by system organ class, the most adverse drug reactions were related to the gastro-intestinal system, followed by psychiatric events. The reported adverse drug reactions for both drugs were more common in women, and the ratio of adverse drug reactions to prescriptions was highest in the elderly. Women aged 19 to 64 years reported more than twice as many adverse drug reactions than men of the same age, and more than 5 times in insomnia., Conclusions: When prescribing montelukast and pranlukast, attention would need to digestive and sleep disorders, especially women aged 19 to 64. After prescribing montelukast, physicians would need to pay more attention to agitation (5/396378 vs 0/82475), bad or vivid dreams (6/396378 vs 0/82475), anxiety (11/396378 vs 0/82475), depression (14/396378 vs 1/82475), tremor (53/396378 vs 7/82475), irritability (5/396378 vs 1/82475), insomnia (159/396378 vs 25/82475), and headache (68/396378 vs 10/82475), compared to when prescribing pranlukast. Further prospective research needs to elucidate the relationship between neuropsychiatric events and montelukast.

Despite the extensive usage of synthetic musk compounds (SMCs) and siloxanes in various personal care products (PCPs), trophic magnification of such chemicals in aquatic environments remains unexplored. In June and September 2020, eleven SMCs and nineteen siloxanes were measured in water, sediments, and biota. Samples were collected from two sites where levels were expected to be influenced by the distance from the wastewater treatment plant (WWTP) in the Geum River, Republic of Korea, were expected. High concentrations of SMCs and siloxanes entered through WWTP were measured in water, sediment, and biota at the both sites and both seasons. The δ 15 N of amino acids provided a high-resolution food web and accurate trophic position (TP), which is an important factor for determining the trophic magnification factor (TMF). Among 24 TMFs, 19 of them were <1, ranging 0.7-0.8 for 1,3,4,6,7,8‑hexahydro‑4,6,6,7,8,8‑hexamethyl‑cyclopenta‑γ‑2‑benzopyran (HHCB), 0.6-0.8 for 6-Acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN), 0.7-0.8 for 4-tert-Butyl-3,5-dinitro-2,6-dimethylacetophenone (MK), 0.7-0.9 for octamethylcyclotetrasiloxane (D4), 0.1-0.4 for decamethylcyclopentasiloxane (D5), and 0.04-0.8 for dodecamethylcyclohexasiloxane (D6), and the remaining ones including HHCB, AHTN, MK, and D4 showed values close to 1 or slightly higher (TMF range: 1.0-2.3) indicating no or a little trophic magnification. The TMFs of these compounds were constant across sites and seasons. The TMF values of PCPs might be affected by species specificity and food web structure rather than by chemical properties such as log K ow , which describes a wide range of TMF values in various environments. This study presents valuable implications for assessing risk and managing environmental fate and trophic transfer of SMCs and siloxanes in freshwater environments., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics., Methods: Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed., Results: The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2., Conclusion: The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

In this study, we identified major aryl hydrocarbon receptor (AhR) agonists in the sediments from Yeongil Bay (n = 6) using effect-directed analysis. Using the H4IIE-luc bioassays, great AhR-mediated potencies were found in aromatic fractions (F2) of sediment organic extracts from silica gel column chromatography and sub-fractions (F2.6-F2.8) from reverse phase-HPLC. Full-scan mass spectrometric analysis using GC-QTOFMS was conducted to identify novel AhR agonists in highly potent fractions, such as F2.6-F2.8 of S1 (Gumu Creek). Selection criteria for AhR-active compounds consisted of three steps, including matching factor of NIST library (≥70), aromatic structures, and the number of aromatic rings (≥4). Fifty-nine compounds were selected as tentative AhR agonist candidates, with the AhR-mediated activity being assessed for six compounds for which standard materials were available commercially. Of these compounds, 20-methylcholanthrene, 7-methylbenz[a]anthracene, 10-methylbenz[a]pyrene, and 7,12-dimethylbenz[a]anthracene exhibited significant AhR-mediated potency. Relative potency values of these compounds were determined relative to benzo[a]pyrene to be 3.2, 1.4, 1.2, and 0.2, respectively. EPA positive matrix factorization modeling indicated that the sedimentary AhR-active aromatic compounds primarily originated from coal combustion and vehicle emissions. Potency balance analysis indicated that four novel AhR agonists explained 0.007% to 1.7% of bioassay-derived AhR-mediated potencies in samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups., Objectives: We aimed to describe the characteristics of SEA and identify its patient subgroups., Methods: Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts., Results: Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/μL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/μL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/μL), and good treatment response in terms of improved lung function and control status., Conclusions: Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted., (© 2021 S. Karger AG, Basel.)

South Korea is one of the largest consumers of flame-retardants worldwide. In this study, water, sediment, and biota samples were collected from a highly industrialized lake to investigate contamination, isomeric profiles, source, and the bioaccumulation potential of hexabromocyclododecanes (HBCDDs). Almost all of the sediments were severely contaminated by HBCDDs, which were some of the highest global levels compared to those found in previous studies. The highest concentrations and similar profiles to those of technical mixtures of HBCDDs were observed in creeks passing through industrial complexes, indicating on-going contamination by high consumption of HBCDDs from industrial activities. γ-HBCDD was dominant in water and sediment, whereas α-HBCDD was dominant in fish and shellfish. The diastereoisomeric profiles of HBCDDs in multiple matrices were influenced by proximity to industry and chemical properties. In-situ biota-sediment accumulation factors of α-HBCDDs were > 1 in benthic species, implying that HBCDDs are of great concern in sedimentary environments., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFASs) are used in industrial and commercial products due to their amphiphilic properties. Birds have been utilized as biomonitoring species due to their environmental pollutant vulnerability and wide distribution. The Oriental Magpie (Pica serica) is a representative residential species inhabiting terrestrial environments. In this study, we measured PFAS concentrations in Magpie liver tissue (n = 253) collected from 12 Korean regions in 2004 and 2017. The predominant compounds were perfluorooctanesulfonic acid (PFOS; mean: 23.8 ng/g wet weight), perfluorotridecanoic acid (PFTrDA; 2.79 ng/g), and perfluoroundecanoic acid (PFUnDA: 2.11 ng/g). We observed significant correlations between Magpie PFAS measurements, indicating similar sources and bioaccumulation processes. Adult females showed significantly lower PFOS concentrations than adult males and young males and females, indicating that avian sex is a crucial physiological factor of PFAS accumulation. PFOS, perfluorodecanoic acid (PFDA), and perfluorotetradecanoic acid (PFTeDA) concentrations in urban regions were significantly higher than rural regions. PFOS concentrations in Magpie livers increased significantly between sampling years, whereas C11-C13 carboxylic acids (PFCAs) decreased. This suggests that urbanization and population are major factors in Magpie PFAS accumulation. Almost all hepatic PFOS concentrations were below the threshold values proposed by previous studies, implying limited risks. Our findings suggest that the Oriental Magpies are PFAS sentinel in residential environments. This is the first comprehensive report on biomonitoring of PFASs using the Oriental Magpie., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Few studies have been conducted on aquatic contamination by alternative plasticizers. Phthalates and novel plasticizers were measured in sediments from a highly industrialized lake to assess occurrence, sources, time trends, and ecological risks. Legacy and alternative plasticizers were detected in all sediments. Di(2-ethylhexyl) phthalate (DEHP) was a predominant plasticizer, indicating its popular industrial consumption for the last two decades. Predominant novel plasticizers were changed over time. The highest sedimentary DEHP level was recorded on the global scale. Legacy and alternative plasticizers in creek sediments significantly increased from 2008 to 2016, while those from inshore and offshore regions of the lake significantly decreased in association with a dilution effect caused by the operation of a tidal power plant. Concentration ratios of alternative plasticizers to DEHP increased for the last decade, implying a shift in consumption of plasticizers. Sedimentary DEHP concentrations in creeks exceeded almost all threshold values associated with ecological risks., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Novel halogenated flame retardants (HFRs) were introduced to industrial markets as alternatives to legacy brominated FRs (BFRs), such as polybrominated diphenyl ethers (PBDEs). In the present study, PBDEs and their brominated and chlorinated alternatives, novel BFRs (NBFRs) and dechlorane plus (DP), were measured in multiple environmental matrices in a highly industrialized lake in Korea. Legacy and novel HFRs were detected in multiple samples, indicating ubiquitous contamination. Concentrations of HFRs in water and sediment observed in creeks running through machine, textiles, and automobile industrial complexes were significantly higher than those observed in inside and outside of the lake. Higher bioaccumulation levels of HFRs were observed in inshore compared with offshore waters. Results suggest that multi-matrix distribution of legacy and novel HFRs was dependent on the geographical proximity to industrial sources. Compared with previous studies, the highest levels of PBDEs and NBFRs were recorded in water samples on a global scale, implying on-going emissions from industrial activities. Decabromodiphenyl ethane (DBDPE) was a dominant compound in water samples, whereas the concentrations of PBDEs, NBFRs, and DP in sediment were similar to each other. This suggests a shift in consumption from legacy to novel HFRs, preferentially in water environments. A significant declining trend in PBDEs was observed in water and sediment collected between 2008 and 2015, indicating the effectiveness of regulatory actions. Based on their environmental occurrence and bioaccumulation potential, pentabromoethylbenzene and bis(2-ethylhexyl) tetrabromophthalate may pose emerging concerns regarding contamination of aquatic environments., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: There are no financial or other issues that might lead to conflict of interest.

Exposure to a single organochlorine pesticide (OCP) at high concentration and over a short period of exposure constrain our understanding of the contribution of chemical exposure to type 2 diabetes (T2D). A total of 450 male and female zebrafish was exposed to mixtures of five OCPs at 0, 0.05, 0.25, 2.5, and 25 μg/L for 12 weeks. T2D-related hematological parameters (i.e., glucose, insulin, free fatty acid, and triglycerides) and mitochondrial complex I to IV activities were assessed. Metabolomics, proteomics, and transcriptomics were analyzed in female livers, and their data-driven integration was performed. High fasting glucose and low insulin levels were observed only at 0.05 μg/L of the OCP mixture in females, indicating a nonlinear and sexually dependent response. We found that exposure to the OCP mixture inhibited the activities of mitochondrial complexes, especially III and IV. Combining individual and integrated omics analysis, T2D-linked metabolic pathways that regulate mitochondrial function, insulin signaling, and energy homeostasis were altered by the OCP mixture, which explains the observed phenotypic hematological effects. We demonstrated the cause-and-effect relationship between exposures to OCP mixture and T2D using zebrafish model. This study gives an insight into mechanistic research of metabolic diseases caused by chemical exposure using zebrafish., (Copyright © 2021 Elsevier B.V. All rights reserved.)