Effect-Directed Analysis Combined with Nontarget Screening to Identify Unmonitored Toxic Substances in the Environment.

Effect-directed analysis (EDA) combined with nontarget screening (NTS) has established a valuable tool for the identification of unmonitored toxic substances in environmental samples. It consists of three main steps: (1) highly potent fraction identification, (2) toxicant candidate selection, and (3) major toxicant identification. Here, we discuss the methodology, current status, limitations, and future challenges of EDA combined with NTS. This method has been applied successfully to various environmental samples, such as sediments, wastewater treatment plant effluents, and biota. We present several case studies and highlight key results. EDA has undergone significant technological advancements in the past 20 years, with the establishment of its key components: target chemical analysis, bioassays, fractionation, NTS, and data processing. However, it has not been incorporated widely into environmental monitoring programs. We provide suggestions for the application of EDA combined with NTS in environmental monitoring programs and management, with the identification of further research needs.

Identification of Mid-Polar and Polar AhR Agonists in Cetaceans from Korean Coastal Waters: Application of Effect-Directed Analysis with Full-Scan Screening.

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 KOA 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.

Objective Assessment of Perioperative Anxiety using Functional Near-infrared Spectroscopy in Elderly Patients: A Prospective Randomized Observational Pilot Study.

Background: Assessing and managing patient anxiety is essential to reduce postoperative complications in elderly patients. However, monitoring patient anxiety objectively is impossible. This study aimed to investigate the correlation between the level of fNIRS signals and anxiety in patients aged 65 and older undergoing artificial joint replacement surgery. Material and Methods: Sixty patients aged ≥65 years scheduled for elective total knee arthroplasty under spinal anesthesia were included. To differentiate the degree of anxiety, the patients were randomly divided into three groups, each consisting of 20 patients (group 1: administered normal saline as a placebo; groups 2 and 3: administered dexmedetomidine at a rate of 0.2 and 0.5 µg/kg/h, respectively, for 10 min). Functional near-infrared spectroscopy was measured continuously for 10 min in each session (session 1: pre-anesthetic period; session 2: immediately after the spinal anesthesia period; session 3: normal saline or dexmedetomidine receiving period) in all patients. Vital signs were measured thrice at 5-min intervals during each session. State-Trait Anxiety Inventory -S (STAI-S) and Ramsay Sedation Scale (RSS) scores were assessed at the end of each session. Results: The STAI-S score was significantly correlated with power of bandwidth (p = 0.034). In addition, the RSS score was significantly correlated with BW 1, 2, and 3 (p = 0.010, p < 0.001, and p = 0.003, respectively). Conclusion: The STAI-S score and BW 3 were significantly correlated, suggesting that fNIRS might help objectively and directly monitor anxiety levels.

Molecular Characterization of Estrogen Receptor Agonists during Sewage Treatment Processes Using Effect-Directed Analysis Combined with High-Resolution Full-Scan Screening.

Endocrine-disrupting potential was evaluated during the sewage treatment process using in vitro bioassays. Aryl hydrocarbon receptor (AhR)-, androgen receptor (AR)-, glucocorticoid receptor (GR)-, and estrogen receptor (ER)-mediated activities were assessed over five steps of the treatment process. Bioassays of organic extracts showed that AhR, AR, and GR potencies tended to decrease through the sewage treatment process, whereas ER potencies did not significantly decrease. Bioassays on reverse-phase high-performance liquid chromatography fractions showed that F5 (log KOW 2.5-3.0) had great ER potencies. Full-scan screening of these fractions detected two novel ER agonists, arenobufagin and loratadine, which are used pharmaceuticals. These compounds accounted for 3.3-25% of the total ER potencies and 4% of the ER potencies in the final effluent. The well-known ER agonists, estrone and 17ß-estradiol, accounted for 60 and 17% of the ER potencies in F5 of the influent and primary treatment, respectively. Fourier transform ion cyclotron resonance mass spectrometry analysis showed that various molecules were generated during the treatment process, especially CHO and CHOS (C: carbon, H: hydrogen, O: oxygen, and S: sulfur). This study documented that widely used pharmaceuticals are introduced into the aquatic environments without being removed during the sewage treatment process.

Newly Identified AhR-Active Compounds in the Sediments of an Industrial Area Using Effect-Directed Analysis.

Effect-directed analysis was used to identify previously unidentified aryl hydrocarbon receptor (AhR) agonists in sediments collected from a highly industrialized area of Ulsan Bay, Korea. The specific objectives were to (i) investigate potent fractions of sediment extracts using the H4IIE-luc bioassay, (ii) determine the concentrations of known AhR agonists (polycyclic aromatic hydrocarbons (PAHs) and styrene oligomers (SOs)), (iii) identify previously unreported AhR agonists in fractions by use of GC-QTOFMS, and (iv) evaluate contributions of individual compounds to overall AhR-mediated potencies, found primarily in fractions containing aromatics with log Kow 5-8. Greater concentrations of PAHs and SOs were also found in those fractions. On the basis of GC-QTOFMS and GC-MSD analyses, 16 candidates for AhR agonists were identified in extracts of sediments. Of these, seven compounds, including 1-methylchrysene, benzo[j]fluoranthene, 3-methylchrysene, 5-methylbenz[a]anthracene, 11H-benzo[b]fluorene, benzo[b]naphtho[2,3-d]furan, and benzo[b]naphtho[2,1-d]thiophene, exhibited significant AhR activity. Relative potency values of newly identified AhR agonists were found to be greater than or comparable to that of benzo[a]pyrene (BaP). The potency balance analysis showed that newly identified AhR agonists explained 0.07-16% of bioassay-derived BaP-EQs. These chemicals were widely distributed in industrial sediments; thus, it is of immediate importance to conduct studies on sources and potential effects of those chemicals.

Interaction of 5-HTT and HTR1A gene polymorphisms in treatment responses to mirtazapine in patients with major depressive disorder.

We tested for the association of HTR1A and 5-HTT genetic polymorphisms with treatment response to mirtazapine and evaluated the interactive effect between the polymorphisms in 283 patients with major depressive disorder. Korean subjects with diagnosis of major depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. Clinical symptoms were evaluated using the 17-item Hamilton Depression Rating (HAMD-17) Scale at baseline and after 1, 2, 4, 8, and 12 weeks of treatment with mirtazapine. The genetic association of 5-HTTLPR and HTR1A+272G>A with treatment response was analyzed. We found a significant association of the 12.12-repeat genotype of 5-HTT various number tandem repeat (VNTR) with a large percentage decline in HAMD-17 Scale score after 4, 8, and 12 weeks of treatment with mirtazapine. We also found that the frequency of the 12.12-repeat genotype was higher in responders than in nonresponders at week 8. The HTR1A+272GG genotype was significantly associated with a large percentage decline in HAMD-17 Scale score at 4, 8, and 12 weeks, although the genotypic frequencies were comparable between responders and nonresponders during the study period. Patients with the 12.12-repeat 5-HTT VNTR and GG of HTR1A+272G>A showed the highest HAMD-17 Scale percentage reduction during the study period and a better treatment response status after 4 weeks. These results suggest that the interaction between HTR1A+272G>A and 5-HTT VNTR is involved in the response to mirtazapine treatment and that a combination of these may be a useful marker for predicting treatment response to mirtazapine.

Preclinical Evidence and Underlying Mechanisms of Polygonum multiflorum and Its Chemical Constituents Against Cognitive Impairments and Alzheimer's Disease.

Objectives: Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of Polygonum multiflorum on cognitive function. Methods: This study focused primarily on the effects of Polygonum multiflorum and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer's disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind Polygonum multiflorum's impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at Polygonum multiflorum's effects on cognitive decline and AD. Results: According to recent research, Poligonum multiflorum and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis. Conclusion: This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of Polygonum multiflorum. We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders.

Chronological distribution and potential sources of persistent toxic substances in soils from the glacier foreland of Midtre Lovénbreen, Svalbard.

Despite its reputation as one of the cleanest regions globally, recent studies have identified the presence of various persistent toxic substances (PTSs) in the environmental matrices collected from Svalbard. This study investigated the chronological distribution and potential sources of 81 PTSs in soils from the glacier foreland of Midtre Lovénbreen. Soil samples (n = 45) were categorized by age based on exposure to the atmosphere due to glacier retreat in July 2014 into five age groups: 80-100 years (n = 7), 60-80 years (n = 12), 40-60 years (n = 16), 20-40 years (n = 7), and <20 years (n = 3). Concentrations of polychlorinated biphenyls (PCBs, n = 32) in soils varied with age, ranging from 0.29 to 0.74 ng g-1 dw. In addition, the concentrations of polycyclic aromatic hydrocarbons (PAHs, n = 28), perylene, and alkyl-PAHs (n = 20) in soils ranged from 21 to 80 ng g-1 dw, 2.9-62 ng g-1 dw, and 73-420 ng g-1 dw, respectively. The concentrations of PTSs were observed to be greater in older soils. Principal component analysis revealed that PCBs in soils originated from various product sources. Positive matrix factorization modeling estimated the association of PAHs in soils with potential origins, such as diesel emissions, petroleum and coal combustion, and coal. Potential sources of PAHs were mainly coal in younger soils and diesel emissions and petroleum combustion in older soils. Alkyl-PAH compositions in the soil were similar to those of bituminous coal, with a noteworthy degree of weathering observed in older soils. The accumulation rate and flux of PTSs in soils exhibited compound-specific patterns, reflecting factors such as long-range transport, fate, origin, and recent inputs. These findings can serve as baseline data for protecting and preserving polar environments.

Increased Right Dorsolateral Prefrontal Cortex Connectivity During Emotion Recognition Task in Adolescents With Self-Injurious Behavior: A Functional Near-Infrared Spectroscopy Study.

OBJECTIVE: Research on neural correlates in the prefrontal cortex (PFC) associated with self-injurious behavior has mainly been performed in adults. However, studies on adolescents are scarce. We aimed to investigate the activation and connectivity of the PFC between adolescents with self-injurious behavior (ASI) and psychiatric controls (PC) using functional near-infrared spectroscopy (fNIRS). METHODS: We used an emotion recognition task during fNIRS to assess 37 adolescents (23 with self-injurious behavior and 14 PC) between June 2020 and October 2021 and compared connectivity and activation between the two groups. We also measured adverse childhood events (ACE, Adverse Childhood Experiences) and performed a correlation analysis of channel activation according to ACE total scores. RESULTS: The difference in activation between the groups was not statistically significant. The connectivity of channel 6 was statistically significant. The interaction between channel 6 and the ACE total score showed statistical significance between the two groups(t[33] -2.61; p=0.014). The ASI group showed a negative correlation with the total ACE score. CONCLUSION: This is the first study to investigate PFC connectivity using fNIRS in ASI. It has the implication of a novel attempt with a practically useful tool to uncover neurobiological differences among Korean adolescents.

Acute effects of (-)-gallocatechin gallate-rich green tea extract on the cerebral hemodynamic response of the prefrontal cortex in healthy humans.

Objective: The benefits of long-term consumption of green tea on the brain are well known. However, among many ingredients of green tea, the acute effects of (-)-gallocatechin gallate-rich green tea extract (GCG-GTE), have received comparatively less attention. Herein, we investigated the acute effects of oral ingestion of green tea with GCG-GTE, which contains close replicas of the ingredients of hot green tea, on task-dependent hemodynamics in the prefrontal cortex of healthy adult human brains. Methods: In this randomized, double-blind, placebo-controlled, parallel group trial, 35 healthy adults completed computerized cognitive tasks that demand activation of the prefrontal cortex at baseline and 1 h after consumption of placebo and 900 mg of GCG-GTE extract supplement. During cognitive testing, hemodynamic responses (change in HbO2 concentration) in the prefrontal cortex were assessed using functional near-infrared spectroscopy (fNIRS). Results: In fNIRS data, significant group x session interactions were found in the left (p = 0.035) and right (p = 0.036) dorsolateral prefrontal cortex (DLPFC). In behavioral data, despite the numerical increase in the GCG-GTE group and the numerical decrease in the Placebo group, no significant differences were observed in the cognitive performance measure between the groups. Conclusion: The result suggests a single dose of orally administered GCG-GTE can reduce DLPFC activation in healthy humans even with increased task demand. GCG-GTE is a promising functional material that can affect neural efficiency to lower mental workload during cognitively demanding tasks. However, further studies are needed to verify this.

Monthly distribution of lipophilic marine biotoxins and associated microalgae in the South Sea Coast of Korea throughout 2021.

Aquaculture farms have been established along the South Sea Coast of Korea, supplying most of the seafood consumed domestically. However, annual harmful algal blooms pose a potential threat to seafood safety. This study aimed to determine the spatial and seasonal distributions of 12 lipophilic marine biotoxins (LMTs) in phytoplankton and mussels in the region in 2021. Solid-phase adsorption toxin tracking (SPATT) was used to monitor the cumulative compositions of LMTs in seawater. LMT concentrations were also determined in twelve commercially available species of domestic shellfish to evaluate the potential risks to human health. Gonyaulux spinifera and Dinophysis acuminata, causative microalgae of yessotoxins (YTXs) and pectenotoxins (PTXs), respectively, showed high densities in the region from May to July. This period corresponded to high LMT concentrations in phytoplankton and mussels. Phytoplankton mainly contained PTX-2 and homo-YTX, with a maximum concentration of 2300 ng g-1 wet weight (ww) in May. In contrast, mussels mainly contained homo-YTX and YTX, with a maximum concentration of 1300 ng g-1 ww in July. LMTs-producing microalgae showed low densities and concentrations after July, whereas mussels accumulated toxins until September. In the SPATT sampler, more diverse LMTs were detected than in seawater, phytoplankton, and mussels. For example, dinophysistoxin-1 and azaspiracid-2 were detected only in SPATT. YTXs were detected in domestic seafood samples, including mussels, red scallops, and pen shells, but the concentrations were below the European Food Safety Agency recommended standard of 3.75 mg YTX-eq. kg-1. Moreover, the hazard quotient was less than 100 in all scenarios, indicating that the human health risk was not significant. This study provides valuable data on monthly distribution patterns of LMTs in the South Sea Coast of Korea and can serve as baseline data for future management policies of marine biotoxins.

Correlation between cerebral hemodynamic functional near-infrared spectroscopy and positron emission tomography for assessing mild cognitive impairment and Alzheimer's disease: An exploratory study.

This study was performed to investigate the usefulness of functional near-infrared spectroscopy (fNIRS) by conducting a comparative analysis of hemodynamic activation detected by fNIRS and positron emission tomography (PET) and magnetic resonance imaging (MRI) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants were divided into four groups: the subjective memory impairment (SMI), amnestic MCI (aMCI), non-amnestic MCI (naMCI), and AD groups. We recorded the hemodynamic response during the semantic verbal fluency task (SVFT) using a commercial wireless continuous-wave NIRS system. The correlation between the parameters of the neuroimaging assessments among the groups was analyzed. Region of interest-based comparisons showed that the four groups had significantly different hemodynamic responses during SVFT in the bilateral dorsolateral prefrontal cortex (DLPFC). The linear mixed effect model result indicates that the mean ΔHbO2 from the bilateral DLPFC regions showed a significant positive correlation to the overall FDG-PET after controlling for age and group differences in the fNIRS signals. Amyloid PET signals tended to better differentiate the AD group from other groups, and fNIRS signals tended to better differentiate the SMI group from other groups. In addition, a comparison between the group pairs revealed a mirrored pattern between the hippocampal volume and hemodynamic response in the DLPFC. The hemodynamic response detected by fNIRS showed a significant correlation with metabolic and anatomical changes associated with disease progression. Therefore, fNIRS may be considered as a screening tool to predict the hemodynamic and metabolic statuses of the brain in patients with MCI and AD.

Characterization of microalgal toxicants in the sediments from an industrial area: Application of advanced effect-directed analysis with multiple endpoint bioassays.

Microalgal toxicants in sediments from an industrialized area (Ulsan Bay) in South Korea were identified using effect-directed analysis (EDA) with full-scan screening analysis (FSA) and microalgal bioassays with multiple endpoints. The growth rate and cell viability of three microalgae (Isochrysis galbana, Dunaliella tertiolecta, and Phaeodactylum tricornutum) were strongly inhibited following exposure to raw organic extracts of sediments from Site D5 (Woehang River). The polar fraction separated using a silica gel column significantly inhibited growth rate, esterase activity, cell membrane intensity, and chlorophyll a autofluorescence. In comparison, non- and mid-polar fractions induced non-toxic or esterase inhibition. Target toxicants, such as polycyclic aromatic hydrocarbons, styrene oligomers, and alkylphenols, were detected at low concentrations (450, 79, and 98 ng g-1 dw, respectively) in the sediment of D5, indicating the presence of unmonitored toxicants. FSA was performed for the polar fraction using LC-QTOFMS, and 31 candidates of toxicants were selected. Toxicological confirmation was conducted for 7 candidates for which standards are available. Out of these, 2-nitrophenol, 3-nitrophenol, and 4-nitrophenol showed significant microalgal toxicity; however, these compounds did not fully explain the induced toxicity. Overall, combining EDA and FSA with multiple endpoint bioassays demonstrated the benefits of characterizing the microalgal toxicants in the environments.

Distributions and potential sources of polychlorinated biphenyls and polycyclic aromatic hydrocarbons in the glacimarine sediments of Arctic Svalbard.

Distribution and sources of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in the glacimarine sediments (35 sites) of Svalbard were investigated. PCBs (32 congeners), traditional PAHs (15 homologs), emerging PAHs (11 homologs), and alkylated PAHs (16 homologs) were widely distributed in the Svalbard sediments (ranges: below method detection limit to 20, 21 to 3600, 1.0 to 1400, and 31 to 15,000 ng g-1 dry weight, respectively). Compositional analysis indicated that PCBs mainly originated from combustion sources, with PAHs being strongly influenced by local sources. Positive matrix factorization analysis showed that PAHs were associated with vehicle and petroleum combustion, coal, and coal combustion. Coal-derived PAHs contributed significantly to the sediments of Van Mijenfjorden. Remnants of coal mining activity trapped in the permafrost appear to enter the coastal environments as ground ice melts. Consequently, PAHs are currently emerging as the most significant contributors to potential risks in the Svalbard ecosystems.

Efficacy of smartphone application-based multi-domain cognitive training in older adults without dementia.

Background: As the population ages and the prevalence of dementia increases, there is a growing emphasis on the importance of cognitive training to prevent dementia. A smartphone application-based cognitive training software program, BeauBrain Trainer (BBT), has been developed to provide better access to cognitive training for older adults. Numerous studies have revealed the effectiveness of cognitive training using a cognitive assessment tool. However, relatively few studies have evaluated brain activation using brain imaging as a result of improved cognitive function. Methods: All participants were required to download the BBT, an Android-based application for cognitive training, onto their own smartphone or tablet computer and to engage in cognitive training at home. Older adults without dementia were enrolled in this study, including 51 participants in the intervention group and 50 participants in the control group. The BBT comprised a set of 12 cognitive tasks, including two tasks in each of the following six cognitive domains: attention, language, calculation, visuospatial function, memory, and frontal/executive function. Each cognitive task was divided into four blocks based on its level of difficulty. A 16-week cognitive training was designed to carry out cognitive tasks using a total of 48 blocks (12 tasks × 4 levels) for at least 1.5 h per day, 5 days per week. All participants in the intervention group were given BBT tasks that gradually increased in difficulty level, which they submitted through a smartphone application daily for 16 weeks. The researchers monitored the participants' task performance records on the website and encouraged participants to engage in cognitive training through regular contact. This study was conducted to investigate the improvement in cognitive function and the activation pattern of the frontal cortex in older adults participating in smartphone application-based cognitive training. The cognitive assessment tool was the BeauBrain cognitive screening test (CST), a tablet-based computerized cognitive screening test. The activation pattern of the frontal cortex was measured using functional near-infrared spectroscopy (fNIRS). Additionally, this study aimed to determine the positive effects of cognitive training on everyday functioning and psychological states using a questionnaire. Results: Of 101 participants, 85 older adults without dementia (84.1%) who completed the study protocol were included in the statistical analysis. There were 41 participants (80.3%) in the intervention group and 44 participants (88.0%) in the control group. A two-way repeated-measures analysis of variance (ANOVA) was used to compare the cognitive scores over a 16-week period between the intervention and control groups. According to the CST results, the intervention group exhibited a statistically significant increase in the language subtest scores, specifically the phonemic word fluency test, compared to those of the control group. The fNIRS results revealed greater activation in the dorsolateral prefrontal cortex during the STROOP incongruent task in the intervention group than did the control group. However, the effectiveness of cognitive training was not observed across a variety of rating scales, including everyday functioning, depression, self-efficacy, attention, and subjective memory complaints. Conclusion: This study revealed that a smartphone-based cognitive training application led to improvements in phonemic generative naming ability and activation of the prefrontal cortex in older adults without dementia. This study is meaningful because it confirmed that cognitive training is partially effective in enhancing frontal lobe function. It also provided information on the brain mechanisms related to the effects of cognitive training using fNIRS.

Instrumental and bioanalytical characterization of dioxin-like activity in sediments from the Yeongsan River and the Nakdong River estuaries, South Korea.

In the present study, we investigated the contamination status of dioxin-like chemicals (DLCs) and potential toxic effects associated with river and coastal sediments from two large estuaries of South Korea. Sediments collected from the Yeongsan River and the Nakdong River estuaries were analyzed for several DLCs, including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), coplanar polychlorinated biphenyls (co-PCBs), and polycyclic aromatic hydrocarbons (PAHs). Greater concentrations of target DLCs (except for PCDDs in Nakdong River) were found in the inland creeks with decreasing trends towards estuarine and coastal areas in both regions. The result indicated that the elevated DLCs were attributable to the surrounding land use activities, such as point sources of industrial and municipal areas from the inland regions. Principal component analysis and positive matrix factorization model revealed that major sources of PCDD/Fs and PAHs in sediments were fly ash and dust, and petroleum and diesel emission, respectively. The dioxin-like activities of the sediments ranged from 0.98 to 88% of the maximal induction elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin, which generally explained the sedimentary contamination by the target DLCs. Dioxin-like activity in sediments from the artificial lake and inland creek of the Nakdong River Estuary was mostly explained by the targeted DLCs (~75%). However, the contribution of known DLCs from the sediments of the Yeongsan River Estuary was relatively low (~35%) compared to that of the Nakdong River Estuary, suggesting the presence of unknown DLCs in sediments. Overall, the distribution of DLCs quite varied by region, generally reflecting the difference in the surrounding land use activity. In the future, it is needed to study the distribution, sources, and potential ecological effects of unknown toxic substances in coastal sediments.

Spatiotemporal distribution characteristics of yessotoxins and pectenotoxins in phytoplankton and shellfish collected from the southern coast of South Korea.

The distribution characteristics of lipophilic marine biotoxins (LMTs), such as yessotoxins (YTXs) and pectenotoxins (PTXs) in phytoplankton, mussels, and commercial seafood were determined for the southern coast of South Korea. Gonyaulax spinifera and Dinophysis acuminata, which are the causative microalgae of YTXs and PTXs, were recorded during summer. Homo-YTX and PTX-2 were predominantly detected in phytoplankton (max: 5.7 µg g-1 ww), whereas only YTXs were detected in mussels (max: 1.1 µg g-1 ww). LMT concentrations in mussels were positively correlated with those in phytoplankton. However, there was a 1-month time gap in maximum LMT concentrations between mussels and phytoplankton. Homo-YTX was detected in commercial seafood, including red scallop and comb pen shell. However, homo-YTX concentrations in shellfish were below the recommended value of the European Food Safety Authority (3.75 mg YTX equivalents kg-1); thus, the consumption of this seafood was not considered to be a significant risk for human health.

Identification of AhR agonists in sediments of the Bohai and Yellow Seas using advanced effect-directed analysis and in silico prediction.

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.

Effect-directed identification of novel aryl hydrocarbon receptor-active aromatic compounds in coastal sediments collected from a highly industrialized area.

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.

Identification of novel polar aryl hydrocarbon receptor agonists accumulated in liver of black-tailed gulls in Korea using advanced effect-directed analysis.

Although bioaccumulation of persistent organic pollutants in seabirds has been examined, few studies have been conducted to identify previously unidentified substances. Here, aryl hydrocarbon receptor (AhR) agonists were identified in livers of black-tailed gulls from South Korea using effect-directed analysis combined with full-scan screening analysis. Significant AhR-mediated potencies were observed in the polar fractions of liver extracts using H4IIE-luc bioassay. Eight known polar AhR agonists accounted for 11-20% of the total AhR-mediated potencies in the polar fractions; hydrocortisone and rutaecarpine were the major contributors. Twenty-two AhR agonist candidates in the polar fractions were identified using liquid chromatography-quadrupole time-of-flight mass spectrometry during a six-step selection process. Of these, [10]-gingerol, angelicin, corticosterone, eupatilin, etofenprox, oxadixyl, and tretinoin were identified as novel AhR agonists. The contribution to potencies increased with inclusion of novel AhR agonists (27-52%); corticosterone and [10]-gingerol contributed significantly. Quantitative structure-activity relationship suggested that the novel AhR agonists have other potential toxic effects, including carcinogenicity and mutagenicity. Polar AhR agonists have been used for pharmaceuticals and pesticides. Some novel AhR agonists have log KOW > 2 and log KOA ≥ 6, which indicates that these compounds can be biomagnified in air-breathing organisms, such as seabirds.