Environmental Toxicology and Chemistry最新文献

{"title":"Computational new approach methods guide focused testing and enhance understanding of chlorantraniliprole toxicity across species.","authors":"Marissa A Jensen-Brickley, Leah Glimsdal, Abigail Johnson, Emma Stacy, Kelvin Santana-Rodriguez, Kali Mattingly, Daniel L Villeneuve, Russ Hockett, Brett Blackwell, Jenna Cavallin, Carlie A LaLone","doi":"10.1093/etojnl/vgae057","DOIUrl":"10.1093/etojnl/vgae057","url":null,"abstract":"<p><p>Diamide insecticides, specifically chlorantraniliprole (CHL), have been rising in popularity over the past decade, becoming one of the most widely used insecticide classes globally. These insecticides target the ryanodine receptor (RyR), primarily for control of lepidopteran agricultural pests. Field studies have revealed that some lepidopteran species have developed mutations where a methionine in a particular position (e.g., I4790M) increases resistance to CHL. The toxicity data for CHL across species is limited, as is the case for many chemicals, which creates an opportunity to apply both traditional toxicity test methods and new approach methods (NAMs) to address data gaps. Here, the U.S. Environmental Protection Agency's Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was used to query the RyR to generate susceptibility predictions for species exposed to CHL to fill those data gaps. These SeqAPASS results generated testable hypotheses that were used to guide focused acute aquatic toxicity studies using Daphnia magna, Daphnia pulex, Pimephales promelas, and Danio rerio. The fish species were not sensitive to CHL, whereas D. magna and D. pulex were found to be sensitive to CHL at environmentally relevant concentrations, despite having the methionine residue in the position of the I4790M resistance mutation. Additional SeqAPASS results showed that many other species, including beneficial pollinators and Lepidoptera, are predicted as likely susceptible to CHL. This study provided multiple lines of evidence toward the unlikelihood for the I4790M mutation to be the primary cause of resistance across species, filled knowledge gaps concerning CHL toxicity across species, and generated predictions of susceptibility for nontarget species that are not generally amenable to toxicity testing. This work presents a case example that demonstrates how NAMs can be used in combination with other types of data to direct targeted testing and build confidence in predictive approaches for their use in risk assessment.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2557-2567"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicogenomic signatures of estrogen-related modes of action in the zebrafish embryo.","authors":"Milena Frelih, Steve U Ayobahan, Fatma Marghany, Fabian Essfeld, Sebastian Eilebrecht","doi":"10.1093/etojnl/vgae059","DOIUrl":"10.1093/etojnl/vgae059","url":null,"abstract":"<p><p>Endocrine disruptors represent a diverse array of chemicals known to interfere with the endocrine systems of both human and environmental organisms, adversely affecting reproduction, development, and behavior, thus raising significant health and ecological concerns. Traditional regulatory tests for endocrine activity typically involve juvenile or adult fish, which is both time-consuming and resource-intensive and necessitates substantial animal use. This study adopts a transcriptomic approach to identify toxicogenomic signatures associated with the disruption of estrogen signaling in zebrafish (Danio rerio) embryos. Utilizing a modified zebrafish embryo toxicity test based on Organisation for Economic Co-operation and Development test guideline 236, the embryos were exposed to two sublethal concentrations of estradiol, bisphenol A, and fulvestrant. Despite no significant effects on survival or hatching rate observed in treated groups compared with the controls, our study effectively pinpointed several genes, including vtg1, cyp19a1b, fam20cl, sult1st2, pck1, agxtb, hsd17b12a, ptgs2a, and ccn1, as linked to a disruption of estrogen signaling. These genes emerge as promising biomarker candidates for identifying and distinguishing estrogen-related modes of action. Additionally, this approach not only supports the detection of potential endocrine disruptors but also opens up possibilities for prioritizing substances for higher tier endocrine testing, which could substantially reduce animal testing in the future.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2568-2579"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing the challenges of acute fish toxicity hazard classification using a non-animal defined approach.","authors":"Donna S Macmillan, Pravin Ambure, Vicente Aranda, Yannick Bayona, Vera Bonderovic, Jay Dawick, Nicolas Fabre, Stephan Fischer, Geoff Hodges, Ágata Llobet-Mut, Sophie Loisel-Joubert, Claudia Rivetti, Jayne Roberts, Kristin Schirmer, Eva Serrano-Candelas, Blanca Serrano Ramón, Ricky A Stackhouse","doi":"10.1093/etojnl/vgaf046","DOIUrl":"10.1093/etojnl/vgaf046","url":null,"abstract":"<p><p>Acute fish toxicity is an ecotoxicological endpoint that provides important information about a chemical's potential to elicit (an) adverse effect(s) on fish. These effects are typically studied using in vivo tests, but for animal welfare reasons as well as the quest for increased species relevance, biological coverage, mechanistic understanding of effects, and throughput, there have been significant efforts in recent years to reduce or replace the use of animals in (eco)toxicological hazard assessment by developing defined approaches (DA) or integrated approaches to testing and assessment. To this end, a novel score-based DA has been developed as a proof-of-concept, which integrates three in silico predictions from freely available (quantitative) structure activity relationship models: the VEGA Fish (KNN-Read-Across) and Fathead Minnow (KNN-IRFMN) models and the United States Environmental Protection Agency ECOSAR Fish 96-h LC50 model, along with in vitro RTgill-W1 data. The DA provides a categorical output aligned with the United Nations Globally Harmonized System of Classification and Labelling framework (Acute Category 1, Acute Category 2, Acute Category 3, or Not Classified) with an overall accuracy of 80%, offering a reliable alternative to traditional in vivo testing methods for acute fish toxicity.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2659-2672"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AOP report: Adverse Outcome Pathway Network for Developmental Androgen Signalling-Inhibition Leading to Short Anogenital Distance in Male Offspring.","authors":"Terje Svingen, Emilie Elmelund, Marie L Holmer, Anna O Bindel, Henrik Holbech, Monica K Draskau","doi":"10.1093/etojnl/vgaf221","DOIUrl":"https://doi.org/10.1093/etojnl/vgaf221","url":null,"abstract":"<p><p>This report outlines an adverse outcome pathway network (AOPN) linking reduced androgen signalling during the fetal masculinization programming window to shortened anogenital distance (AGD) at birth. In mammals such as mice, rats, and humans, the AGD is approximately twice as long in males as in females, driven by androgen-dependent differentiation of the male phenotype. Impaired androgen signalling during fetal development can lead to a significantly shorter AGD in male offspring, a sexually dimorphic feature widely used in rodent toxicity studies and human epidemiological research to assess exposure to anti-androgenic substances. AGD measurement is an endpoint in several OECD Test Guideline studies for reproductive toxicity. Notably, androgen signalling can be perturbed by various molecular initiating events, and capturing these causal toxicological pathways may facilitate the use of non-animal test data to help inform predictive toxicology by describing the mechanistic knowledge required for hazard and risk assessment of chemicals. The AOPN includes three AOPs all converging on the same adverse outcome of 'reduced AGD' but with distinct upstream pathways. The upstream portion of the AOPN includes more generalized key events (KEs) and key event relationships (KERs) with broad applicability domains, many of which are measurable by well-established in vitro methods. In contrast, the downstream events have a narrower applicability domain, focusing on development of the perineal region and AGD in male offspring. This report provides overall assessments of AOPs 305, 306, and 307, including one new KE (2298) and four new KERs (2127, 3448, 3449, 3349) not previously reported. The overall confidence for all three AOPs are moderate-to-high with few inconsistencies or uncertainties. The taxonomic domain of the AOPN is mammals, with most evidence coming from mouse, rat and human studies. The upstream network capturing the molecular events has broad taxonomic applicability to all mammals and could likely be extended to some other vertebrates.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Zebrafish embryo-based test system for thyroid hormone system disruption: 3Rs in ecotoxicological research.","authors":"Lisa Gölz, Melanie Blanc-Legendre, Maximilian Rinderknecht, Laura Behnstedt, Sara Coordes, Luisa Reger, Sacha Sire, Xavier Cousin, Thomas Braunbeck, Lisa Baumann","doi":"10.1002/etc.5878","DOIUrl":"10.1002/etc.5878","url":null,"abstract":"<p><p>There is increasing concern regarding pollutants disrupting the vertebrate thyroid hormone (TH) system, which is crucial for development. Thus, identification of TH system-disrupting chemicals (THSDCs) is an important requirement in the Organisation for Economic Co-operation and Development (OECD) testing framework. The current OECD approach uses different model organisms for different endocrine modalities, leading to a high number of animal tests. Alternative models compatible with the 3Rs (replacement, reduction, refinement) principle are required. Zebrafish embryos, not protected by current European Union animal welfare legislation, represent a promising model. Studies show that zebrafish swim bladder inflation and eye development are affected by THSDCs, and the respective adverse outcome pathways (AOPs) have been established. The present study compared effects of four THSDCs with distinct molecular modes of action: Propylthiouracil (PTU), potassium perchlorate, iopanoic acid, and the TH triiodothyronine (T3) were tested with a protocol based on the OECD fish embryo toxicity test (FET). Effects were analyzed according to the AOP concept from molecular over morphological to behavioral levels: Analysis of thyroid- and eye-related gene expression revealed significant effects after PTU and T3 exposure. All substances caused changes in thyroid follicle morphology of a transgenic zebrafish line expressing fluorescence in thyrocytes. Impaired eye development and swimming activity were observed in all treatments, supporting the hypothesis that THSDCs cause adverse population-relevant changes. Findings thus confirm that the FET can be amended by TH system-related endpoints into an integrated protocol comprising molecular, morphological, and behavioral endpoints for environmental risk assessment of potential endocrine disruptors, which is compatible with the 3Rs principle.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2485-2502"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using molecular dynamics simulation to enhance conservation analysis for cross species extrapolation of the PFOA-transthyretin interaction.","authors":"Dylan J Buglewicz, Ryan Staub, Daniel T Chang, Stefania Evoli, Peter G Schumann, Alexander R Cole, Jennifer H Olker, Carlie A LaLone","doi":"10.1093/etojnl/vgaf160","DOIUrl":"10.1093/etojnl/vgaf160","url":null,"abstract":"<p><p>The U.S. Environmental Protection Agency's web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was developed to evaluate protein conservation across species through sequence and structural alignments to gather lines of evidence for predicting chemical susceptibility. Although SeqAPASS can rapidly generate predictions of species susceptibility in terms of a \"yes\" or \"no\" output, there is a growing interest in deriving more quantitative metrics for enhancing these predictions. To do this, a bioinformatics workflow was developed that combined SeqAPASS results with molecular docking and molecular dynamics (MD) simulations. This workflow was developed using transthyretin (TTR) and a per- and polyfluoroalkyl substance, with an emphasis on perfluorooctanoic acid (PFOA) as it is known that PFOA binds to TTR in humans and other experimental animals. This workflow was applied to generate quantitative information as additional lines of evidence for the conservation of the PFOA-TTR interaction across species. The SeqAPASS analysis predicted hundreds of species as susceptible based on conservation of the PFOA-TTR interaction (Level 1: 952 species, Level 2: 976 species, Level 3: 750 species). Predicted TTR structures from a subset of the species predicted as susceptible by SeqAPASS were used in molecular docking and MD simulations. The simulations supported that Lysine-15 is a key residue for the PFOA-TTR interaction. Quantitatively there was no significant difference in the species tested regarding their predicted binding affinities or other metrics specific to the chemical-protein interactions. These results demonstrated that the interaction between TTR and PFOA is likely conserved across various vertebrate taxonomic groups. Overall, this work provides a template for how advanced bioinformatics tools like MD simulations can be applied within ecotoxicology for improving cross-species predictions of chemical susceptibility. Importantly, our efforts aim to demonstrate applicability of these computational methods for integration in next-generation risk assessments.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2687-2702"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity of 19 pesticides in rainbow trout gill, liver, and intestinal cell lines.","authors":"Sophie Emberley-Korkmaz, Krittika Mittal, Na'im Temlock, Jessica Head, Niladri Basu","doi":"10.1002/etc.5808","DOIUrl":"10.1002/etc.5808","url":null,"abstract":"<p><p>The rainbow trout gill cell line (RTgill-W1), via test guideline 249 of the Organisation for Economic Co-operation and Development, has been established as a promising New Approach Methodology, although to advance confidence in the method more case studies are needed that: 1) expand our understanding of applicability domains (chemicals with diverse properties); 2) increase methodological throughput (96-well format); and 3) demonstrate biological relevance (in vitro to in vivo comparisons; gill vs. other cells). Accordingly, the objective of our study was to characterize the cytotoxicity of 19 pesticides against RTgill-W1 cells, and also liver (RTL-W1) and gut epithelial (RTgutGC) cell lines, and then to compare the in vitro and in vivo data. Of the 19 pesticides tested, 11, 9, and 8 were cytotoxic to the RTgill-W1, RTL-W1, and RTgutGC cells, respectively. Six pesticides (carbaryl, chlorothalonil, chlorpyrifos, dimethenamid-P, metolachlor, and S-metolachlor) were cytotoxic to all three cell lines. Aminomethylphosphonic acid, chlorantraniliprole, dicamba, diquat, imazethapyr, and permethrin exhibited cell-line-specific toxicity. No cytotoxic responses were observed for three herbicides (atrazine, glyphosate, and metribuzin) and four insecticides (clothianidin, diazinon, imidacloprid, and thiamethoxam). When cytotoxicity was measured, there was a strong correlation (rs = 0.9, p < 0.0001) between in vitro median effect concentration (EC50) values (based on predicted concentrations using the In Vitro Mass Balance Model Equilibrium Partitioning (IV-MBM EQP) Ver. 2.1) derived from RTgill-W1 and RTL-W1 cells with in vivo median lethal concentration (LC50) values from 96-h acute toxicity studies with trout. In all 28 cases, the in vitro EC50 was within 18-fold of the in vivo LC50. These data help increase our understanding of the ecotoxicological domains of applicability for in vitro studies using cultured rainbow trout cells, while also demonstrating that these assays performed well in a 96-well format and have promise to yield data of biological relevance.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2443-2454"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative glucocorticoid receptor agonism: In silico, in vitro, and in vivo and identification of potential biomarkers for synthetic glucocorticoid exposure.","authors":"Alexander R Cole, Brett R Blackwell, Jenna E Cavallin, Jacob E Collins, Ashley R Kittelson, Yesmeena M Shmaitelly, Laura M Langan, Daniel L Villeneuve, Bryan W Brooks","doi":"10.1093/etojnl/vgae041","DOIUrl":"10.1093/etojnl/vgae041","url":null,"abstract":"<p><p>The glucocorticoid receptor (GR) is present in almost every vertebrate cell and is utilized in many biological processes. Despite an abundance of mammalian data, the structural conservation of the receptor and cross-species susceptibility, particularly for aquatic species, has not been well defined. Efforts to reduce, refine, and/or replace animal testing have increased, driving the impetus to advance development of new approach methodologies (NAMs). Here we used in silico, in vitro, and in vivo methods to elucidate a greater understanding of receptor-mediated effects of synthetic glucocorticoid exposure in teleost fish. Evolutionary conservation of amino acid residues critical for transcriptional activation was confirmed in silico using sequence alignment to predict across species susceptibility. Subsequent in vitro assays using zebrafish and human GR provided evidence of physiological congruence of GR agonism. Finally, adult fathead minnows (Pimephales promelas) were exposed in vivo to the synthetic glucocorticoids, dexamethasone (0.04, 400, 4,000 µg/L) and beclomethasone dipropionate (130 µg/L), and GR agonism confirmed via digital polymerase chain reaction; in addition, EcoToxChip analyses identified potential mRNA biomarkers following glucocorticoid exposure. These findings support the use of NAMs to potentially reduce multispecies in vivo experimentation while providing empirical evidence that expands the taxonomic domain of applicability for the GR agonism molecular initiating event within the broader GR agonism adverse outcome pathway network.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2545-2556"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A combination of high-throughput in vitro and in silico new approach methods for ecotoxicology hazard assessment for fish.","authors":"Jo Nyffeler, Felix R Harris, Clinton Willis, Gabrielle Byrd, Brett Blackwell, Beate I Escher, Alex Kasparek, John Nichols, Jonathan T Haselman, Grace Patlewicz, Daniel L Villeneuve, Joshua A Harrill","doi":"10.1093/etojnl/vgae083","DOIUrl":"10.1093/etojnl/vgae083","url":null,"abstract":"<p><p>Fish acute toxicity testing is used to inform environmental hazard assessment of chemicals. In silico and in vitro approaches have the potential to reduce the number of fish used in testing and increase the efficiency of generating data for assessing ecological hazards. Here, two in vitro bioactivity assays were adapted for use in high-throughput chemical screening. First, a miniaturized version of the Organisation for Economic Co-operation and Development (OECD) test guideline 249 plate reader-based acute toxicity assay in RTgill-W1 cells was developed. Second, the Cell Painting (CP) assay was adapted for use in RTgill-W1 cells along with an imaging-based cell viability assay. Then, 225 chemicals were tested in each assay. Potencies and bioactivity calls from the plate reader and imaging-based cell viability assays were comparable. The CP assay was more sensitive than either cell viability assay in that it detected a larger number of chemicals as bioactive, and phenotype altering concentrations (PACs) were lower than concentrations that decreased cell viability. An in vitro disposition (IVD) model that accounted for sorption of chemicals to plastic and cells over time was applied to predict freely dissolved PACs and compared with in vivo fish toxicity data. Adjustment of PACs using IVD modeling improved concordance of in vitro bioactivity and in vivo toxicity data. For the 65 chemicals where comparison of in vitro and in vivo values was possible, 59% of adjusted in vitro PACs were within one order of magnitude of in vivo toxicity lethal concentrations for 50% of test organisms. In vitro PACs were protective for 73% of chemicals. This combination of in vitro and in silico approaches has the potential to reduce or replace the use of fish for in vivo toxicity testing.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2599-2621"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gap between human toxicology and ecotoxicology under one health perspective by a cross-species adverse outcome pathway network for reproductive toxicity.","authors":"Elizabeth Dufourcq Sekatcheff, Jaeseong Jeong, Jinhee Choi","doi":"10.1002/etc.5940","DOIUrl":"10.1002/etc.5940","url":null,"abstract":"<p><p>Although ecotoxicological and toxicological risk assessments are performed separately from each other, recent efforts have been made in both disciplines to reduce animal testing and develop predictive approaches instead, for example, via conserved molecular markers, and in vitro and in silico approaches. Among them, adverse outcome pathways (AOPs) have been proposed to facilitate the prediction of molecular toxic effects at larger biological scales. Thus, more toxicological data are used to inform on ecotoxicological risks and vice versa. An AOP has been previously developed to predict reproductive toxicity of silver nanoparticles via oxidative stress on the nematode Caenorhabditis elegans (AOPwiki ID 207). Following this previous study, our present study aims to extend the biologically plausible taxonomic domain of applicability (tDOA) of AOP 207. Various types of data, including in vitro human cells, in vivo, and molecular to individual, from previous studies have been collected and structured into a cross-species AOP network that can inform both human toxicology and ecotoxicology risk assessments. The first step was the collection and analysis of literature data to fit the AOP criteria and build a first AOP network. Then, key event relationships were assessed using a Bayesian network modeling approach, which gave more confidence in our overall AOP network. Finally, the biologically plausible tDOA was extended using in silico approaches (Genes-to-Pathways Species Conservation Analysis and Sequence Alignment to Predict Across Species Susceptibility), which led to the extrapolation of our AOP network across over 100 taxonomic groups. Our approach shows that various types of data can be integrated into an AOP framework, and thus facilitates access to knowledge and prediction of toxic mechanisms without the need for further animal testing.</p>","PeriodicalId":11793,"journal":{"name":"Environmental Toxicology and Chemistry","volume":" ","pages":"2511-2523"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}