Frontiers in toxicology最新文献

{"title":"Ergot alkaloid control in biotechnological processes and pharmaceuticals (a mini review).","authors":"A Volnin, A Parshikov, N Tsybulko, P Mizina, N Sidelnikov","doi":"10.3389/ftox.2024.1463758","DOIUrl":"https://doi.org/10.3389/ftox.2024.1463758","url":null,"abstract":"<p><p>The control of ergot alkaloids in biotechnological processes is important in the context of obtaining new strain producers and studying the mechanisms of the biosynthesis, accumulation and secretion of alkaloids and the manufacturing of alkaloids. In pharmaceuticals, it is important to analyze the purity of raw materials, especially those capable of racemization, quality control of dosage forms and bulk drugs, stability during storage, etc. This review describes the methods used for qualitative and quantitative chemical analysis of ergot alkaloids in tablets and pharmaceutic forms, liquid cultural media and mycelia from submerged cultures of ergot and other organisms producing ergoalkaloid, sclerotias of industrial <i>Claviceps spp</i>. parasitic strains. We reviewed analytical approaches for the determination of ergopeptines (including their dihydro- and bromine derivatives) and semisynthetic ergot-derived medicines such as cabergoline, necergoline and pergolide, including precursors for their synthesis. Over the last few decades, strategies and approaches for the analysis of ergoalkaloids for medical use have changed, but the general principles and objectives have remained the same as before. These changes are related to the development of new genetically improved strains producing ergoalkaloids and the development of technologies for the online control of biotechnological processes and pharmaceutical manufacturing (\"process analytical technologies,\" PAT). Overall, the industry is moving toward \"smart manufacturing.\" The development of approaches to production cost estimation and product quality management, manufacturing management, increasing profitability and reducing the negative impact on personnel and the environment are integral components of sustainable development. Analytical approaches for the analysis of ergot alkaloids in pharmaceutical raw materials should have high enough specificity for the separation of dihydro derivatives, enantiomers and R-S epimers of alkaloids, but low values of the quantitative detection limit are less frequently needed. In terms of methodology, detection methods based on mass spectrometry have become more developed and widespread, but NMR analysis remains in demand because of its high accuracy and specificity. Both rapid methods and liquid chromatography remain in demand in routine practice, with rapid analysis evolving toward higher accuracy owing to improved analytical performance and new equipment. New composite electrochemical sensors (including disposable sensors) have demonstrated potential for real-time process control.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1463758"},"PeriodicalIF":3.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New approach methodologies (NAMs) for the <i>in vitro</i> assessment of cleaning products for respiratory irritation: workshop report.","authors":"Lynne T Haber, Mark A Bradley, Amanda N Buerger, Holger Behrsing, Sabina Burla, Phillip W Clapp, Scott Dotson, Casey Fisher, Keith R Genco, Francis H Kruszewski, Shaun D McCullough, Kathryn E Page, Vivek Patel, Nathan Pechacek, Clive Roper, Monita Sharma, Annie M Jarabek","doi":"10.3389/ftox.2024.1431790","DOIUrl":"https://doi.org/10.3389/ftox.2024.1431790","url":null,"abstract":"<p><p>The use of <i>in vitro</i> new approach methodologies (NAMs) to assess respiratory irritation depends on several factors, including the specifics of exposure methods and cell/tissue-based test systems. This topic was examined in the context of human health risk assessment for cleaning products at a 1-day public workshop held on 2 March 2023, organized by the American Cleaning Institute^® (ACI). The goals of this workshop were to (1) review <i>in vitro</i> NAMs for evaluation of respiratory irritation, (2) examine different perspectives on current challenges and suggested solutions, and (3) publish a manuscript of the proceedings. Targeted sessions focused on exposure methods, <i>in vitro</i> cell/tissue test systems, and application to human health risk assessment. The importance of characterization of assays and development of reporting standards was noted throughout the workshop. The exposure methods session emphasized that the appropriate exposure system design depends on the purpose of the assessment. This is particularly important given the many dosimetry and technical considerations affecting relevance and translation of results to human exposure scenarios. Discussion in the <i>in vitro</i> cell/tissue test systems session focused on the wide variety of cell systems with varying suitability for evaluating key mechanistic steps, such as molecular initiating events (MIEs) and key events (KEs) likely present in any putative respiratory irritation adverse outcome pathway (AOP). This suggests the opportunity to further develop guidance around <i>in vitro</i> cell/tissue test system endpoint selection, assay design, characterization and validation, and analytics that provide information about a given assay's utility. The session on applications for human health protection emphasized using mechanistic understanding to inform the choice of test systems and integration of NAMs-derived data with other data sources (e.g., physicochemical properties, exposure information, and existing <i>in vivo</i> data) as the basis for <i>in vitro</i> to <i>in vivo</i> extrapolation. In addition, this group noted a need to develop procedures to align NAMs-based points of departure (PODs) and uncertainty factor selection with current human health risk assessment methods, together with consideration of elements unique to <i>in vitro</i> data. Current approaches are described and priorities for future characterization of <i>in vitro</i> NAMs to assess respiratory irritation are noted.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1431790"},"PeriodicalIF":3.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of the toxic potential of parabens in fish.","authors":"Asok K Dasmahapatra, Joydeep Chatterjee, Paul B Tchounwou","doi":"10.3389/ftox.2024.1399467","DOIUrl":"10.3389/ftox.2024.1399467","url":null,"abstract":"<p><p>Parabens are the most prevalent ingredients in cosmetics and personal care products (PCPs). They are colorless and tasteless and exhibit good stability when combined with other components. Because of these unique physicochemical properties, they are extensively used as antimicrobial and antifungal agents. Their release into the aquatic ecosystem poses potential threats to aquatic organisms, including fish. We conducted an electronic search in PubMed (http://www.ncbi.nlm.nih.gov/pubmed) using the search term parabens and fish and sorted 93 articles consisting of methyl paraben (MTP), ethyl paraben (ETP), propyl paraben (PPP), butyl paraben (BTP), and benzyl paraben (BNP) in several fish species. Furthermore, we confined our search to six fish species (common carp, <i>Cyprinus carpio</i>; fathead minnows, <i>Pimephales promelas</i>; Japanese medaka, <i>Oryzias latipes</i>; rainbow trout, <i>Oncorhynchus mykiss</i>; Nile tilapia, <i>Oreochromis niloticus</i>; and zebrafish, <i>Danio rerio)</i> and four common parabens (MTP, ETP, PPP, and BTP) and sorted 48 articles for review. Our search indicates that among all six fish, zebrafish was the most studied fish and the MTP was the most tested paraben in fish. Moreover, depending on the alkyl chain length and linearity, long-chained parabens were more toxic than the parabens with short chains. Parabens can be considered endocrine disruptors (EDs), targeting estrogen-androgen-thyroid-steroidogenesis (EATS) pathways, blocking the development and growth of gametes, and causing intergenerational toxicity to impact the viability of offspring/larvae. Paraben exposure can also induce behavioral changes and nervous system disorders in fish. Although the USEPA and EU limit the use of parabens in cosmetics and pharmaceuticals, their prolonged persistence in the environment may pose an additional health risk to humans.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1399467"},"PeriodicalIF":3.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application and interpretation of immunophenotyping data in safety and risk assessment.","authors":"Victor J Johnson, Michael I Luster, Andrew Maier, Corey Boles, Eric W Miller, Daniel E Arrieta","doi":"10.3389/ftox.2024.1409365","DOIUrl":"10.3389/ftox.2024.1409365","url":null,"abstract":"<p><p>The use of immunophenotyping during immunotoxicity investigations was first popularized in the 1980 s and has since become more integrated into diagnostic and non-clinical assessments. The data provided from immunophenotyping can serve as an initial source of information to guide decisions for additional, more advanced, immunotoxicity testing as well as for human health safety and risk assessment of drugs and chemicals. However, comprehensive guidance describing applications of immunophenotyping data in immunotoxicity investigations is lacking, particularly among regulatory bodies. Therefore, a critical examination is needed for the appropriate interpretations and potential misinterpretations of such data during the assessment of drug safety and chemical risk. As such, the current uses and implications of immunophenotyping data in human health safety and risk assessments has been evaluated to provide additional context for the application of current methodologies and guidelines. In addition, case studies are presented to highlight the challenges of interpreting immunophenotyping results along with incorporating the findings into immunotoxicity investigations. Based on the analyses of current approaches and methodologies, a decision flow is presented for use of immunophenotyping data during risk informed decision making.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1409365"},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fulfilling the criteria for CLP classification: the implications for substances under the EU chemicals legislation.","authors":"Diana Kättström, Anna Beronius, Urban Boije Af Gennäs, Christina Rudén, Marlene Ågerstrand","doi":"10.3389/ftox.2024.1452065","DOIUrl":"https://doi.org/10.3389/ftox.2024.1452065","url":null,"abstract":"<p><p>The CLP mandates manufacturers and importers to classify substances and mixtures according to hazard criteria, with notifications submitted to the European Chemicals Agency (ECHA). Substances meeting hazard criteria must be appropriately labelled and packaged to communicate hazards effectively. The CLP establishes hazard classification criteria but does not independently prohibit or restrict the use of hazardous chemicals. Instead, it serves as a basis for regulatory obligations in other specific regulations. This study investigates the regulatory implications of meeting hazard criteria under the CLP across EU regulations and directives listed in EU Chemicals Legislation Finder (EUCLEF). The results show that fulfilling criteria for human health hazard classes trigger regulatory obligations in the highest number of regulations/directives, with carcinogenicity, mutagenicity, and reproductive toxicity (CMR) leading to obligations in 19 of 20 pieces of legislation linked to the CLP. Conversely, physical, environmental, and ozone layer hazards are associated with fewer regulations and directives, and lead to fewer prohibitions. The study underscores the pivotal role of the CLP in EU chemical legislation and the need for coherence and consistency across regulations. While regulatory obligations are primarily aimed at substances meeting hazard criteria, the variability in self-classification notifications and limitations in harmonized classification processes were observed. Moreover, the complexity of the regulatory structure poses challenges for stakeholders and policymakers, including inconsistencies, compliance difficulties, and the need for frequent revisions. Addressing these challenges is critical for enhancing regulatory effectiveness and ensuring a more coherent and harmonized approach to chemical management in the EU.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1452065"},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonicotinoid pesticides: evidence of developmental neurotoxicity from regulatory rodent studies.","authors":"Jennifer Beth Sass, Nathan Donley, William Freese","doi":"10.3389/ftox.2024.1438890","DOIUrl":"https://doi.org/10.3389/ftox.2024.1438890","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Neonicotinoids are the most widely used class of insecticides in the United States (U.S.). and the world. Consistent with their high use and persistence, neonicotinoids are often found contaminating drinking water and food. They are also detected in human urine, breast milk, amniotic and cerebrospinal fluids, as well as the brains of treated rodents. Neonicotinoids were once thought to pose little neurotoxic risk to humans, but a growing body of research challenges that assumption. In this study we provide the first comprehensive assessment of unpublished rodent developmental neurotoxicity (DNT) studies on five neonicotinoids that were submitted to the U.S. Environmental Protection Agency (EPA) by neonicotinoid manufacturers. Groups of female rats were administered three different doses of a neonicotinoid during pregnancy and lactation, and their offspring subjected to various neurological tests and brain measurements. We identified nicotine-like effects such as reduced brain size, indicative of neuronal cell loss. Statistically significant shrinkage of brain tissue was observed in high-dose offspring for five neonicotinoids: acetamiprid, clothianidin, imidacloprid, thiacloprid, and thiamethoxam. Two brain regions reduced in the rodent studies-the corpus callosum and caudate-putamen-tend to be smaller in people diagnosed with attention-deficit hyperactivity disorder (ADHD), and in children of mothers who smoked during pregnancy, suggesting a possible link between perinatal neonicotinoid exposure and ADHD. A decreased auditory startle reflex was reported for acetamiprid at all doses and was statistically significant in the mid- and high-dose offspring, and for clothianidin in juvenile high-dose females. No mid- or low-dose brain morphometric data were submitted for acetamiprid, imidacloprid, or thiacloprid. Thiamethoxam mid- and low-dose brain morphometric data were provided to EPA upon request. Only partial mid-dose brain morphometry data were submitted for clothianidin, but no low-dose data. Yet despite this lack of data, EPA concluded that only the high-dose brain morphometric effects were treatment-related-setting the mid-dose as the study's No Observed Adverse Effect Level (NOAEL) or failing to find a definitive NOAEL for acetamiprid, clothianidin, imidacloprid, thiacloprid and thiamethoxam. We found numerous deficiencies in EPA's regulatory oversight and data analyses. EPA dismissed statistically significant adverse effects, accepted substandard DNT studies despite lack of valid positive control data, and allowed neonicotinoid registrants to unduly influence agency decision-making. We conclude that perinatal exposure to neonicotinoids and their metabolites induces adverse, nicotine-like neurotoxic effects in rodent bioassays, and that the exposure limits set by EPA for human exposure are either not protective or not supported by available neurotoxicity data. We propose regulatory changes to empower EPA to better protect public health f","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1438890"},"PeriodicalIF":3.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the effects of cannabidiol and a CBD-rich hemp extract in <i>Caenorhabditis elegans</i>.","authors":"Jessica A Camacho, Bonnie Welch, Martine Ferguson, Estatira Sepehr, Cory Vaught, Yang Zhao, Suzanne Fitzpatrick, Jeffrey Yourick, Robert L Sprando, Piper Reid Hunt","doi":"10.3389/ftox.2024.1469341","DOIUrl":"https://doi.org/10.3389/ftox.2024.1469341","url":null,"abstract":"<p><p>Consumer use of cannabidiol (CBD) is growing, but there are still data gaps regarding its possible adverse effects on reproduction and development. Multiple pathways and signaling cascades involved in organismal development and neuronal function, including endocannabinoid synthesis and signaling systems, are well conserved across phyla, suggesting that <i>Caenorhabditis elegans</i> can model the <i>in vivo</i> effects of exogenous cannabinoids. The effects in <i>C. elegans</i> on oxidative stress response (OxStrR), developmental timing, juvenile and adult spontaneous locomotor activity, reproductive output, and organismal CBD concentrations were assessed after exposure to purified CBD or a hemp extract suspended in 0.5% sesame oil emulsions. In <i>C. elegans</i>, this emulsion vehicle is equivalent to a high-fat diet (HFD). As in mammals, HFD was associated with oxidative-stress-related gene expression in <i>C. elegans</i> adults. CBD reduced HFD-induced OxStrR in transgenic adults and counteracted the hypoactivity observed in HFD-exposed wild-type adults. In <i>C. elegans</i> exposed to CBD from the onset of feeding, delays in later milestone acquisition were irreversible, while later juvenile locomotor activity effects were reversible after the removal of CBD exposure. CBD-induced reductions in mean juvenile population body size were cumulative when chronic exposures were initiated at parental reproductive maturity. Purified CBD was slightly more toxic than matched concentrations of CBD in hemp extract for all tested endpoints, and both were more toxic to juveniles than to adults. Dosimetry indicated that all adverse effect levels observed in <i>C. elegans</i> far exceeded recommended CBD dosages for humans.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1469341"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Workflow for predictive risk assessments of UVCBs: cheminformatics library design, QSAR, and read-across approaches applied to complex mixtures of metal naphthenates.","authors":"A J Prussia, C Welsh, T S Somers, P Ruiz","doi":"10.3389/ftox.2024.1452838","DOIUrl":"https://doi.org/10.3389/ftox.2024.1452838","url":null,"abstract":"<p><p>Substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) are commonly found in the environment. However, assessing their human toxicological risk is challenging due to their variable composition and many constituents. Metal naphthenate salts are one such category of UVCBs that are the reaction products of naphthenic acids with metals to form complex mixtures. Metal naphthenates are often found or used in household and industrial materials with potential for human exposure, but very few of these materials have been evaluated for causing human health hazards. Herein, we evaluate metal naphthenates using predictions derived from read-across and quantitative structure-activity/property relationship (QSAR/QSPR) models. Accordingly, we first built a computational chemistry library by enumerating the structures of naphthenic acids and derived 11,850 QSAR-acceptable structures; then, we used open and commercial <i>in silico</i> tools on these structures to predict a set of physicochemical properties and toxicity endpoints. We then compared the QSAR/QSPR predictions with available experimental data on naphthenic acids to provide a more complete picture of the contributions of the components to the toxicity profiles of metal naphthenate mixtures. The available systematic acute oral toxicity values (LD₅₀) and QSAR LD₅₀ predictions of all the naphthenic acid components indicated low concern for toxicity. The point of departure predictions for chronic repeated dose toxicity for the naphthenic acid components using QSAR models developed from studies on rats ranged from 25 to 50 mg/kg/day. These values are in good agreement with findings from studies on copper and zinc naphthenates, which had no observed adverse effect levels of 30 and 118 mg/kg/day, respectively. Hence, this study demonstrates how published <i>in silico</i> approaches can be used to identify the potential components of metal naphthenates for further testing, inform groupings of UVCBs such as naphthenates, as well as fill the data gaps using read-across and QSAR models to inform risk assessment.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1452838"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential mammary carcinogens used in food contact articles: implications for policy, enforcement, and prevention.","authors":"Lindsey V Parkinson, Birgit Geueke, Jane Muncke","doi":"10.3389/ftox.2024.1440331","DOIUrl":"https://doi.org/10.3389/ftox.2024.1440331","url":null,"abstract":"<p><p>Many nations have food contact material (FCM) legislation purporting to protect citizens from hazardous chemicals, often specifically by regulating genotoxic carcinogens. Despite such regulations, cancers that are associated with harmful chemical exposures are highly prevalent, especially breast cancer. Using the novel Key Characteristics of Toxicants framework, Kay et al. found 921 substances that are potential mammary carcinogens. By comparing Kay et al.'s chemicals list with our own Database on migrating and extractable food contact chemicals (FCCmigex), we found that 189 (21%) of the potential mammary carcinogens have been measured in FCMs. When limiting these results to migration studies published in 2020-2022, 76 potential mammary carcinogens have been detected to migrate from FCMs sold in markets across the globe, under realistic conditions of use. This implies that chronic exposure of the entire population to potential mammary carcinogens from FCMs is the norm and highlights an important, but currently underappreciated opportunity for prevention. Reducing population-wide exposure to potential mammary carcinogens can be achieved by science-based policy amendments addressing the assessment and management of food contact chemicals.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1440331"},"PeriodicalIF":3.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cocktail effects of clothianidin and imidacloprid in zebrafish embryonic development, with high and low concentrations of mixtures.","authors":"Seonggeun Zee, Moonjung Hyun, Hee-Jung Sim, Kanghee Kim, Ju-Chan Kang, Chang-Beom Park","doi":"10.3389/ftox.2024.1464069","DOIUrl":"10.3389/ftox.2024.1464069","url":null,"abstract":"<p><p>There is growing concern that sprayed neonicotinoid pesticides (<i>neonics</i>) persist in mixed forms in the environmental soil and water systems, and these concerns stem from reports of increase in both the detection frequency and concentration of these pollutants. To confirm the toxic effects of <i>neonics</i>, we conducted toxicity tests on two <i>neonics</i>, clothianidin (CLO) and imidacloprid (IMD), in embryos of zebrafish. Toxicity tests were performed with two different types of mixtures: potential mixture compounds and realistic mixture compounds. Potential mixtures of CLO and IMD exhibited synergistic effects, in a dose-dependent manner, in zebrafish embryonic toxicity. Realistic mixture toxicity tests that are reflecting the toxic effects of mixture in the aquatic environment were conducted with zebrafish embryos. The toxicity of the CLO and IMD mixture at environmentally-relevant concentrations was confirmed by the alteration of the transcriptional levels of target genes, such as cell damage linked to oxidative stress response and thyroid hormone synthesis related to zebrafish embryonic development. Consequently, the findings of this study can be considered a strategy for examining mixture toxicity in the range of detected environmental concentrations. In particular, our results will be useful in explaining the mode of toxic action of chemical mixtures following short-term exposure. Finally, the toxicity information of CLO and IMD mixtures will be applied for the agricultural environment, as a part of chemical regulation guideline for the use and production of pesticides.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1464069"},"PeriodicalIF":3.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}