Treatment of an accident of imidacloprid poisoning.

Objective: Accidental oral imidacloprid poisoning occurred in a family in Shandong, China, in May 2023. This study aimed to analyze the clinical characteristics of this imidacloprid poisoning event and investigated the detection of toxicants. Methods: Clinical data of four patients with oral imidacloprid poisoning were collected and retrospectively analyzed. The relevant literature was then reviewed. Results: Four patients from the same family received different oral doses of imidacloprid. The main clinical manifestations were digestive and neurological symptoms, including nausea, vomiting, and varying degrees of consciousness. Laboratory tests showed an increased white blood cell count, neutrophil proportion, and mild elevation of transaminase and urea nitrogen levels in some patients. Following comprehensive treatment, which included hemoperfusion, gastric lavage, total gastrointestinal decontamination, and drug symptomatic treatment, the patient's symptoms were quickly relieved, and the concentration of imidacloprid in the blood rapidly decreased. Conclusion: Toxicant detection is an important criterion for the differential diagnosis of poisoning and is helpful for disease assessment, treatment plan formulation, and in determining patient prognosis.

High-efficiency effect-directed analysis (EDA) advancing toxicant identification in aquatic environments: Latest progress and application status.

Facing the great threats to ecosystems and human health posed by the continuous release of chemicals into aquatic environments, effect-directed analysis (EDA) has emerged as a powerful tool for identifying causative toxicants. However, traditional EDA shows problems of low-coverage, labor-intensive and low-efficiency. Currently, a number of high-efficiency techniques have been integrated into EDA to improve toxicant identification. In this review, the latest progress and current limitations of high-efficiency EDA, comprising high-coverage effect evaluation, high-resolution fractionation, high-coverage chemical analysis, high-automation causative peak extraction and high-efficiency structure elucidation, are summarized. Specifically, high-resolution fractionation, high-automation data processing algorithms and in silico structure elucidation techniques have been well developed to enhance EDA. While high-coverage effect evaluation and chemical analysis should be further emphasized, especially omics tools and data-independent mass acquisition. For the application status in aquatic environments, high-efficiency EDA is widely applied in surface water and wastewater. Estrogenic, androgenic and aryl hydrocarbon receptor-mediated activities are the most concerning, with causative toxicants showing the typical structural features of steroids and benzenoids. A better understanding of the latest progress and application status of EDA would be beneficial to further advance in the field and greatly support aquatic environment monitoring.

Does pyrethroid exposure lower human semen quality? a systematic review and meta-analysis.

Background: Pyrethroids are natural organic compounds extracted from flowers of pyrethrums and commonly used as domestic and commercial insecticides. Although it is effective in insect and parasitic control, its associated toxicity, including spermotoxicity, remains a challenge globally. Currently, the available reports on the effect of pyrethroids on semen quality are conflicting, hence an evaluation of its detrimental effect is pertinent. This study conducts a detailed systematic review and meta-analysis of the effects of pyrethroids on sperm quality. Materials and methods: The present study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a pre-defined strategic protocol, an internet search was done using combined text words. The criteria for eligibility were selected based on Population, Exposure, Comparator, Outcome, and Study Designs (PECO) framework, and relevant data were collected. Appraisal was done using The Office of Health Assessment and Translation (OHAT) tool for the evaluation of the Risk of Bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines for the certainty of evidence. A quantitative meta-analysis was conducted with the Review Manager (RevMan). Results: Only 12 out of the 4, 050 studies screened were eligible for inclusion in this study. The eligible studies were from China (4), Japan (3), Poland (3), and United States (2). All the eligible studies were cross-sectional. A total of 2, 050 male subjects were included in the meta-analysis. Pyrethroid exposure significantly reduced sperm motility. Region-stratified subgroup analyses revealed that pyrethroid significantly reduced sperm motility among men in Poland and United States, and decreased sperm count among men in Japan. Pyrethroid exposure also reduced sperm concentration among men in Poland but increased sperm concentration among men in the United States. Conclusion: Although the study revealed inconsistent evidence on the detrimental effect of pyrethroids on semen quality, the findings showed that pyrethroids have deleterious potentials on sperm motility, count, and concentration. Studies focusing on the assessment of semen quality in pyrethroid-exposed men, especially at specific varying levels of exposure, and employing prospective cohort studies or controlled cross-sectional designs are recommended.

Occurrence and Prioritization of Human Androgen Receptor Disruptors in Sewage Sludges Across China.

The global practice of reusing sewage sludge in agriculture and its landfill disposal reintroduces environmental contaminants, posing risks to human and ecological health. This study screened sewage sludge from 30 Chinese cities for androgen receptor (AR) disruptors, utilizing a disruptor list from the Toxicology in the 21st Century program (Tox21), and identified 25 agonists and 33 antagonists across diverse use categories. Predominantly, natural products 5α-dihydrotestosterone and thymidine emerged as agonists, whereas the industrial intermediate caprolactam was the principal antagonist. In-house bioassays for identified disruptors displayed good alignment with Tox21 potency data, validating employing Tox21 toxicity data for theoretical toxicity estimations. Potency calculations revealed 5α-dihydrotestosterone and two pharmaceuticals (17ß-trenbolone and testosterone isocaproate) as the most potent AR agonists and three dyes (rhodamine 6G, Victoria blue BO, and gentian violet) as antagonists. Theoretical effect contribution evaluations prioritized 5α-dihydrotestosterone and testosterone isocaproate as high-risk AR agonists and caprolactam, rhodamine 6G, and 8-hydroxyquinoline (as a biocide and a preservative) as key antagonists. Notably, 16 agonists and 20 antagonists were newly reported in the sludge, many exhibiting significant detection frequencies, concentrations, and/or toxicities, demanding future scrutiny. Our study presents an efficient strategy for estimating environmental sample toxicity and identifying key toxicants, thereby supporting the development of appropriate sludge management strategies.

High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

The Enigma of Norbormide, a Rattus-Selective Toxicant.

Norbormide (NRB) is a Rattus-selective toxicant, which was serendipitously discovered in 1964 and formerly marketed as an eco-friendly rodenticide that was deemed harmless to non-Rattus species. However, due to inconsistent efficacy and the emergence of second-generation anticoagulants, its usage declined, with registration lapsing in 2003. NRBs' lethal action in rats entails irreversible vasoconstriction of peripheral arteries, likely inducing cardiac damage: however, the precise chain of events leading to fatality and the target organs involved remain elusive. This unique contractile effect is exclusive to rat arteries and is induced solely by the endo isomers of NRB, hinting at a specific receptor involvement. Understanding NRB's mechanism of action is crucial for developing species-selective toxicants as alternatives to the broad-spectrum ones currently in use. Recent research efforts have focused on elucidating its cellular mechanisms and sites of action using novel NRB derivatives. The key findings are as follows: NRB selectively opens the rat mitochondrial permeability transition pore, which may be a factor that contributes to its lethal effect; it inhibits rat vascular KATP channels, which potentially controls its Rattus-selective vasoconstricting activity; and it possesses intracellular binding sites in both sensitive and insensitive cells, as revealed by fluorescent derivatives. These studies have led to the development of a prodrug with enhanced pharmacokinetic and toxicological profiles, which is currently undergoing registration as a novel efficacious eco-sustainable Rattus-selective toxicant. The NRB-fluorescent derivatives also show promise as non-toxic probes for intracellular organelle labelling. This review documents in more detail these developments and their implications.

Exploring the impact of polystyrene microplastics on human health: unravelling the health implications of polystyrene microplastics (PS-MPs): a comprehensive study on cytotoxicity, reproductive health, human exposure, and exposure assessment.

This investigation explores the various impacts that polystyrene microplastics (PS-MPs) have on human health. As most of the plastic materials affect human health when they release leachable toxic substances that affect human health, this causes a negative effect that determines poor health conditions and leads to health hazards associated with plastic toxins routed in the human body, such as: Polychlorinated Biphenyls, Polybrominated Biphenyls etc. The study includes micro-plastic exposure assessment on testicular structure analysis, and cytotoxicity evaluations of different human cell types. The findings clarified the possible dangers of PS-MPs exposure from food, medications, and common products, emphasising the necessity of standard specimen handling procedures for precise biomonitoring.

Dynamical analysis of a diffusive population-toxicant model with toxicant-taxis in polluted aquatic environments.

This paper deals with a diffusive population-toxicant model in polluted aquatic environments, with a toxicant-taxis term describing a toxicant-induced behavior change, that is, the population tends to move away from locations with high-level toxicants. The global existence of solutions is established by the techniques of the semigroup estimation and Moser iteration. Based on a detailed study on the properties of the principal eigenvalue for non-self-adjoint eigenvalue problems, we investigated the local and global stability of the toxin-only steady-state solution and the existence of positive steady state, which yields sufficient conditions that lead to population persistence or extinction. Finally, by numerical simulations, we studied the effects of some key parameters, such as toxicant-taxis coefficient, advection rate, and effect coefficient of the toxicant on population growth, on population persistence. Both numerical and analytical results show that a weak chemotaxis effect, a small advection rate of the population, and a weak effect of the toxicant on population growth are favorable for population persistence.

Assessment of Mitochondrial Function in the AmE-711 Honey Bee Cell Line: Boscalid and Pyraclostrobin Effects.

There is a growing concern that chronic exposure to fungicides contributes to negative effects on honey bee development, life span, and behavior. Field and caged-bee studies have helped to characterize the adverse outcomes (AOs) of environmentally relevant exposures, but linking AOs to molecular/cellular mechanisms of toxicity would benefit from the use of readily controllable, simplified host platforms like cell lines. Our objective was to develop and optimize an in vitro-based mitochondrial toxicity assay suite using the honey bee as a model pollinator, and the electron transport chain (ETC) modulators boscalid and pyraclostrobin as model fungicides. We measured the effects of short (~30 min) and extended exposures (16-24 h) to boscalid and pyraclostrobin on AmE-711 honey bee cell viability and mitochondrial function. Short exposure to pyraclostrobin did not affect cell viability, but extended exposure reduced viability in a concentration-dependent manner (median lethal concentration = 4175 µg/L; ppb). Mitochondrial membrane potential (MMP) was affected by pyraclostrobin in both short (median effect concentration [EC50] = 515 µg/L) and extended exposure (EC50 = 982 µg/L) scenarios. Short exposure to 10 and 1000 µg/L pyraclostrobin resulted in a rapid decrease in the oxygen consumption rate (OCR), approximately 24% reduction by 10 µg/L relative to the baseline OCR, and 64% by 1000 µg/L. Extended exposure to 1000 µg/L pyraclostrobin reduced all respiratory parameters (e.g., spare capacity, coupling efficiency), whereas 1- and 10-µg/L treatments had no significant effects. The viability of AmE-711 cells, as well as the MMP and cellular respiration were unaffected by short and extended exposures to boscalid. The present study demonstrates that the AmE-711-based assessment of viability, MMP, and ETC functionality can provide a time- and cost-effective platform for mitochondrial toxicity screening relevant to bees. Environ Toxicol Chem 2024;43:976-987. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

[Development of an analytical system for dried blood spots for forensic toxicology: a case study of five common drugs and poisons].

Dried blood spot (DBS) technology is a simple and convenient method for collecting, transporting, and storing blood samples on filter paper, and has numerous applications in the clinical, research, and public health settings. This technique is gaining popularity in the field of forensic science because it facilitates the rapid analysis of prohibited drugs in blood samples and offers significant advantages in toxicology scenarios such as drinking-driving screening, drug abuse detection, and doping detection. However, the lack of a standardized system and the fact that its stability and reliability have not been thoroughly researched and demonstrated limit its application in judicial practice in China. DBS samples can be prepared, stored, and analyzed in various ways, all of which may significantly affect the results. In this study, we developed a method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) that focuses on the preparation, pretreatment, analysis, and storage of DBS samples. A thorough investigation was conducted to examine the optimal preparation conditions, including the blood spot matrix, drying technique, and preprocessing parameters, such as the solvent and extraction method. Moreover, the analytical conditions, such as the mobile phase system and elution gradient, were established to facilitate the quantitative detection of methamphetamine, lidocaine, ketamine, fentanyl, and diazepam in both DBS and whole-blood samples. The impact of storage conditions, such as the temperature, humidity, and sealing, on the analytical results of the DBS and whole-blood samples was also examined. The results showed a strong linear relationship for lidocaine and fentanyl within the range of 0.5-100 ng/mL. Similarly, methamphetamine, ketamine, and diazepam exhibited good linearity within the range of 2-100 ng/mL. The coefficients of determination (r2) ranged from 0.9983 to 0.9997, and the limits of detection ranged from 0.2 to 0.5 ng/mL, indicating a high degree of correlation and sensitivity. Stability tests demonstrated that the five target substances remained stable in the DBS for 60 days, with the measured contents deviating from the nominal values by 15%. Moreover, the measurement results of the DBS samples were highly similar to those of the whole-blood samples, with mean percentage differences of 4.44%, 3.50%, 7.66%, 5.10%, and 5.25% for fentanyl, diazepam, ketamine, lidocaine, and methamphetamine, respectively. Throughout the 60-day storage period, the maintenance of temperatures of -20 and 4 ℃, as well as sealing and dry storage, was not necessary. Room temperature was the most practical storage environment for the DBS samples. The results for each target showed very small concentration differences between the whole-blood and DBS samples, indicating that the DBS samples were suitable for drug and poison analysis in blood. Furthermore, the DBSs exhibited high quantitative consistency with the whole-blood samples, rendering them suitable matrices for preserving blood samples. Because DBS samples are easy to handle and store, they can realize the lightweight preservation of blood samples and provide a novel solution for the analysis and preservation of blood samples in public security practice. We recommend conducting comprehensive validations before utilizing DBS for analysis, particularly in terms of quantification, to ensure the judicial reliability of the results.

Integrated In-Silico and In Vitro analysis to Decipher the contribution of bisphenol-A in cervical cancer.

Bisphenol A (BPA) is a synthetic chemical widely used as a monomer for producing polycarbonate plastics. The present investigation employed an in-silico approach to identify BPA-responsive genes and comprehend the biological functions affected using in vitro studies. A Comparative Toxicogenomics Database search identified 29 BPA-responsive genes in cervical cancer (CC). Twenty-nine genes were screened using published datasets, and thirteen of those showed differential expression between normal and CC samples. Protein-Protein Interaction Networks (PPIN) analysis identified BIRC5, CASP8, CCND1, EGFR, FGFR3, MTOR, VEGFA, DOC2B, WNT5A, and YY1 as hub genes. KM-based survival analysis identified that CCND, EGFR, VEGFA, FGFR3, DOC2B, and YY1 might affect CC patient survival. SiHa and CaSki cell proliferation, migration, and invasion were all considerably accelerated by BPA exposure. Changes in cell morphology, remodeling of the actin cytoskeleton, increased number and length of filopodia, elevated intracellular reactive oxygen species and calcium, and lipid droplet accumulation were noted upon BPA exposure. BPA treatment upregulated the expression of epithelial to mesenchymal transition pathway members and enhanced the nuclear translocation of CTNNB1. We showed that the enhanced migration and nuclear translocation of CTNNB1 upon BPA exposure is a calcium-dependent process. The present study identified potential BPA-responsive genes and provided novel insights into the biological effects and mechanisms affected by BPA in CC. Our study raises concern over the use of BPA.

Rice straw-derived chitosan-enhanced plasticizers as biologically and environmentally friendly alternatives for sustainable materials.

Plasticizers like Bis(2-ethylhexyl)phthalate (DEHP) are commonly used to enhance plastic properties but pose environmental and health risks. This study successfully derived plasticizers X and Y from rice straws, demonstrating efficacy in chitosan polymer coatings. Chitosan-based polymers exhibit exceptional hardness, with a value of 300 MPa, due to their enriched structure and robust chitosan bonding. This surpasses the hardness of DEHP. Zebrafish exposure over 5 days revealed that X and Y had no significant behavioral impact, while DEHP caused noticeable toxic effects. Maternal DEHP exposure reduced placental cell growth, unlike X and Y, which had no adverse effects on uterine differentiation or placenta formation, suggesting their safety in human pregnancy. The successful development of X and Y represents a crucial step towards greener plasticizers, addressing environmental concerns and promoting safer alternatives in various industries.

Seasonal efficacy and risks from a sodium nitrite toxic bait for wild pigs.

BACKGROUND: Wild pigs (Sus scrofa) are an invasive and destructive species throughout many regions of the world. A sodium nitrite (SN) toxic bait is currently used in Australia and being developed for use in the US and other countries to combat the increasing populations of wild pigs. In the US, efforts to modify the Australian SN-toxic bait and baiting strategy have focused on reducing issues with non-target animals accessing the SN-toxic bait spilled outside of bait stations by wild pigs. We tested and compared modifications for efficacy (with wild pigs) and hazards (with non-targets) in north-central Texas, US during summer (July 2021) and winter (March 2023) seasons. RESULTS: During both seasons we found that visitation to the bait sites declined 94-99% after deploying the SN-toxic bait, and we found a total of 106 dead wild pigs, indicating considerable lethality for the local population. Prior to deploying the SN-toxic bait, Global Positioning System (GPS)-collared wild pigs were more likely to cease visiting bait sites during summer when foraging resources were abundant. Farrowing decreased visitation to bait sites during the winter. We observed no dead non-targets during summer; winter results showed an average of 5.2 dead migrating birds per bait site (primarily Dark-eye juncos [Junco hyemalis]) from consuming SN-toxic bait spilled by wild pigs. The presence and winter-foraging behaviors of migrating birds appeared to increase hazards for those species. CONCLUSION: The current formulation of SN-toxic bait was effective at removing wild pigs during both seasons, however it is clear that different baiting strategies may be required in winter when migrating birds are present. Baiting wild pigs prior to farrowing during the winter, and during drier summers, may further improve efficacy of the bait. Reducing hazards to non-targets could be achieved by refining the SN-toxic bait or modifying bait stations to decrease the potential for spillage, decreasing environmental persistence if spilled, or decreasing attractiveness to migrating birds. © 2024 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Suitability of containerized toxicant to control Solenopsis invicta (Hymenoptera: Formicidae) threatening cave species in Bexar County, Texas.

Several protected troglobitic invertebrate species are known to occur in caves on Joint Base San Antonio-Camp Bullis, Bexar County, Texas, United States. The United States Fish and Wildlife Service (USFWS) identified red-imported fire ant Solenopsis invicta (hereafter RIFA) (Buren 1972) as the primary threat to cave species' nutrient sources, cave crickets, Ceuthophilus secretus (Scudder 1894). Per the service's recommendations, Joint Base San Antonio-Camp Bullis currently implements boiling water mound injections with digging for RIFA control. However, treatment effectiveness is highly variable and largely dependent on the time of day, weather, and personnel diligence. Toxicants have been used for RIFA treatment throughout the world, but concerns exist that traditional applications of toxicant bait around caves might be accessible and inadvertently affect nontarget arthropods, including cricket populations. To mitigate this accessibility, physically limiting access to the toxicant from crickets may be an option. Our objectives were to (i) compare and evaluate the effectiveness of Amdro (Hydramethylnon) and Advion (Indoxacarb) granular baits housed in Ants-No-More Bait Stations (Kness MFG. Inc., Albia, IA) and (ii) evaluate the distance of effectiveness of each bait within a bait station. Ultimately, we observed a 98% reduction in RIFA mound abundance from both baits. Additionally, RIFA mounds within 10 m of the containerized toxicant were reduced by 70%. Our pilot study suggested that Ants-No-More Bait Stations are an effective way to reduce RIFA mounds by 70% if placed 10 m from each other. In practice, this could include bait stations completely covering a particular distance to a cave entrance or fewer bait stations in a ring barrier at a single radial distance to a cave entrance. Containerized toxicants may be a cost-effective and safe RIFA control option around protected cave environments, but further studies are needed to determine potential effects on nontarget arthropods, optimal bait station configuration, and potential effects of biomagnification.

Zooplankton taxa repository of DDTtot and sumPCB14: Seasonal and decadal variations in Lake Maggiore.

Lake Maggiore has been the subject of a monitoring program on persistent organic pollutants (DDTs and PCBs) since 1996 when DDT contamination was first detected. In this context, in 2009 we started to estimate the concentration of DDTtot (Dichlorodiphenyltrichloroethane, sum of p,p'-DDT, o,p'-DDT, p,p'-DDD, o,p-DDD, p,p-DDE, o,p-DDE) and sumPCB14 (polychlorinated biphenyls 18, 28, 31, 44, 52, 101, 118, 149, 138, 153, 170, 180, 194 and 209) in zooplankton pelagic organisms preyed on by zooplanktivorous fish (size fraction ≥450 µm). We evaluated taxa specific repositories of DDTtot and sumPCB14, their seasonal variation, their changes over the period 2009-2021 and the potential contribution of different taxa in transferring toxicants to whitefish, based on the Ivlev's Electivity Index. The repository of both POPs was generally higher in spring. A decrease in the zooplankton Standing Stock Biomass (SSB) drove a decline in the zooplankton DDTtot repository over the last six years (2016-2021 SSBmean = 12.5 mg m-3; 2009-2015; SSBmean = 30 mg m-3), despite the concentration being broadly constant during this period. The sumPCB14 repository was generally characterized by lower values during the last six years, but the difference with the previous period was not so marked. Daphnia and cyclopoids were the major contributors to the repository; however, when the whitefish selectivity index was applied, the role of carnivorous Bythotrephes was more important to the detriment of cyclopoids, particularly in summer and winter. Our results are useful to elaborate predictive models on the transfer of POPs along the food chain and highlight not only the importance of freshwater zooplankton in toto, but also that different taxa can have different roles. The increasing importance of microphagous zooplankton, driven by water warming and extended thermal stratification, underlines the need for future studies on the role of small zooplankton as carriers of POPs in freshwater lakes.

Effect-Directed Analysis Based on Transthyretin Binding Activity of Per- and Polyfluoroalkyl Substances in a Contaminated Sediment Extract.

Only a fraction of the total number of per- and polyfluoroalkyl substances (PFAS) are monitored on a routine basis using targeted chemical analyses. We report on an approach toward identifying bioactive substances in environmental samples using effect-directed analysis by combining toxicity testing, targeted chemical analyses, and suspect screening. PFAS compete with the thyroid hormone thyroxin (T4 ) for binding to its distributor protein transthyretin (TTR). Therefore, a TTR-binding bioassay was used to prioritize unknown features for chemical identification in a PFAS-contaminated sediment sample collected downstream of a factory producing PFAS-coated paper. First, the TTR-binding potencies of 31 analytical PFAS standards were determined. Potencies varied between PFAS depending on carbon chain length, functional group, and, for precursors to perfluoroalkyl sulfonic acids (PFSA), the size or number of atoms in the group(s) attached to the nitrogen. The most potent PFAS were the seven- and eight-carbon PFSA, perfluoroheptane sulfonic acid (PFHpS) and perfluorooctane sulfonic acid (PFOS), and the eight-carbon perfluoroalkyl carboxylic acid (PFCA), perfluorooctanoic acid (PFOA), which showed approximately four- and five-times weaker potencies, respectively, compared with the native ligand T4 . For some of the other PFAS tested, TTR-binding potencies were weak or not observed at all. For the environmental sediment sample, not all of the bioactivity observed in the TTR-binding assay could be assigned to the PFAS quantified using targeted chemical analyses. Therefore, suspect screening was applied to the retention times corresponding to observed TTR binding, and five candidates were identified. Targeted analyses showed that the sediment was dominated by the di-substituted phosphate ester of N-ethyl perfluorooctane sulfonamido ethanol (SAmPAP diester), whereas it was not bioactive in the assay. SAmPAP diester has the potential for (bio)transformation into smaller PFAS, including PFOS. Therefore, when it comes to TTR binding, the hazard associated with this substance is likely through (bio)transformation into more potent transformation products. Environ Toxicol Chem 2024;43:245-258. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Gene-Environment Interactions: My Unique Journey.

I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have authored/coauthored more than 600 publications in the fields of clinical medicine, biochemistry, biophysics, pharmacology, drug metabolism, toxicology, molecular biology, cancer, standardized gene nomenclature, developmental toxicology and teratogenesis, mouse genetics, human genetics, and evolutionary genomics. Looking back, I think my career can be divided into four distinct research areas, which I summarize mostly chronologically in this article: (a) discovery and characterization of the AHR/CYP1 axis, (b) pharmacogenomics and genetic prediction of response to drugs and other environmental toxicants, (c) standardized drug-metabolizing gene nomenclature based on evolutionary divergence, and (d) discovery and characterization of the SLC39A8 gene encoding the ZIP8 metal cation influx transporter. Collectively, all four topics embrace gene-environment interactions, hence the title of my autobiography.

An integrated in vitro approach to identifying chemically induced oxidative stress and toxicity in mitochondria.

Growing concerns exist about increasing chemical usage and the potential health risks. Developing an efficient strategy to evaluate or predict the toxicity of chemicals is necessary. The mitochondria are essential organelles for cell maintenance and survival but also serve as one of the main targets of toxic chemicals. Mitochondria play an important role in the pathology of respiratory disease, and many environmental chemicals may induce impairment of the respiratory system through mitochondrial damage. This study aimed to develop integrated in vitro approaches to identify chemicals that could induce adverse health effects by increasing mitochondria-mediated oxidative stress using the H441 cells, which have a club-cell-like phenotype. Twenty-six environmental toxicants (biocides, phthalates, bisphenols, and particles) were tested, and each parameter was compared with eleven reference compounds. The inhibitory concentrations (IC20 and IC50) and benchmark doses (BMD) of the tested compounds were estimated from three in vitro assays, and the toxic concentration was determined. At the lowest IC20, the effects of compounds on mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were compared. Principal component analysis and k-mean clustering were performed to cluster the chemicals that had comparable effects on the cells. Chemicals that induce mitochondrial damage at different concentrations were used for an in-depth high-tier assessment and classification as electron transport system (ETS) uncoupling or inhibiting agents. Additionally, using in vitro to in vivo extrapolation (IVIVE) tools, equivalent administration doses and maximum plasma concentrations of tested compounds in human were estimated. This study suggests an in vitro approach to identifying mitochondrial damage by integrating several in vitro toxicity tests and calculation modeling.

Chemical Intolerance and Mast Cell Activation: A Suspicious Synchronicity.

Background: Chemical Intolerance (CI) is characterized by intolerances for chemicals, foods, and drugs with multi-system symptoms. As yet, the biomechanism remains unclear. One study reported converging lines of evidence supporting a substantive association between mast cell activation syndrome (MCAS) and CI. The purpose of this study is to (1) confirm a previous report demonstrating that 60% of MCAS patients report CI and (2) examine the parallels between symptoms and intolerances in CI and MCAS. Methods: Five hundred forty-four MCAS patients were assigned a clinical MCAS score using a validated assessment instrument and were assessed for CI using the validated Quick Environmental Exposure Sensitivity Index. Results: Our outcomes confirm the previously published study where the majority of MCAS patients also have CI. There was a clear overlap between various ICD-10 diagnostic categories and CI symptoms, providing further support for a potential shared mechanism. Conclusions: Exposures to pesticides, volatile organic compounds, combustion products, and mold have previously been reported as initiators of CI. However, until recently, little was known about the biological mechanism involved that could explain the multisystem symptoms associated with CI. This paper addresses a newly identified biomechanism for disease, which may underlie a host of "medically unexplained symptoms" triggered by xenobiotics.

Comparison of Biomarkers of Exposure in a Controlled Study of Smokers Switched from Conventional Cigarettes to Heated Tobacco Products.

The heated tobacco product (HTP) heats rather than burns tobacco to release an aerosol with significantly fewer toxicants than conventional cigarette smoke and has received global attention in recent years. To investigate whether changes in biomarkers of exposure could be detected after switching from conventional cigarettes (CCs) to HTPs, 224 subjects from four cities in China participated in this study. Nine biomarkers containing tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and the biomarkers for acrolein and crotonaldehyde were determined by UPLC-MS/MS. The levels of the sum of nine biomarkers in CCs were 5.4 and 5.2 times higher than in an Original-HTP and Menthol-HTP, respectively. Among the nine biomarkers, 3HPMA and 3HMPMA accounted for the highest proportions. Switching from CCs to HTPs is good for both men and women because the changes in each biomarker in urine samples were the same in men and women. Among all the subjects, subjects aged 20-39 years had the greatest reduction in biomarker residues in urine. The findings of the present study provided useful information for the health risk research of HTPs in China.