{"title":"Are glyphosate or glyphosate-based herbicides linked to metabolic dysfunction-associated steatotic liver disease (MASLD)? The weight of current evidence","authors":"Luana Riechelmann-Casarin , Leticia Cardoso Valente , Rosemari Otton , Luís Fernando Barbisan , Guilherme Ribeiro Romualdo","doi":"10.1016/j.etap.2025.104705","DOIUrl":"10.1016/j.etap.2025.104705","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30 % of the world’s population, increasing its prevalence by 50 % in the last three decades. MASLD pathogenesis is considered multiaxial, involving disturbances in the liver, adipose tissue (AT), and gut microbiome. In parallel with MASLD increasing trends, the total herbicide use has nearly tripled over the last three decades. Glyphosate (GLY) is the most used herbicide worldwide (825 mi kg/year). The intensive use of GLY-based herbicides (GBH) – largely driven by the adoption of glyphosate-tolerant genetically modified crops over the past two decades - has led to environmental (soil and water) and food contamination, resulting in continuous human exposure. Emerging (pre)clinical data highlights the significant implications of this herbicide on MASLD, marking a critical research area. Thus, this narrative review paper aimed at gathering and evaluating all epidemiological and (pre)clinical data on the implications of GLY or GBH on MASLD outcomes. Our work encompassed literature published between 2008–2025. Human urinary GLY levels are associated with different MASLD outcomes (steatosis risk, advanced fibrosis, increased transaminases) and comorbidities (higher risk for metabolic syndrome, diabetes, obesity and cardiovascular diseases) (6 studies). <em>In vitro</em> data indicate that GBH/GLY cause oxidative stress, genomic instability, apoptosis, and membrane disruption in hepatocytes, while promoting apoptosis and lipid peroxidation in (pre)adipocytes and cytokine production in monocytes (15 studies). In rodent studies (21 studies), GLY/GBH - in doses based on human exposure/toxicological limits - induces inflammatory and oxidative responses in the liver and AT, while causing dysbiosis and metabolic alterations in the gut microbiome axis. In the light of populational-, cell- and animal-based evidence, GLY/GBH disturbs key axis of MASLD pathogenesis and is hypothesized to be associated with its clinical outcomes.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104705"},"PeriodicalIF":4.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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":"Evaluation of the interaction between the pesticides chlorantraniliprole and imidacloprid with the ATP-binding cassette transporter G2 (ABCG2): In vitro and in vivo assays","authors":"Esther Blanco-Paniagua , Indira Álvarez-Fernández , Laura Álvarez- Fernández , Alicia Millán-García , Gracia Merino","doi":"10.1016/j.etap.2025.104709","DOIUrl":"10.1016/j.etap.2025.104709","url":null,"abstract":"<div><div>Pesticides used in agriculture to control pests can also affect non-target animals, such as livestock and humans, through exposure. Pesticide residues found in animal-derived products like milk serve as evidence of exposure in mammals and may pose health risks due to bioaccumulation. Understanding the mechanisms of elimination and toxicity of pesticides is essential to minimize their negative impact. The ATP-binding cassette (ABC) transporter ABCG2 is a membrane protein involved in xenobiotic biodisposition and milk secretion. Our purpose was to evaluate its role in the in vitro transport and secretion into milk of two pesticides: chlorantraniliprole and imidacloprid. Using MDCK–II cells transduced with ABCG2, we found that they are effectively transported by murine, ovine and bovine ABCG2. In vivo studies using wild-type and Abcg2<sup>-/-</sup> mice showed that milk concentration of chlorantraniliprole was affected by Abcg2, potentially leading to toxicological effects and contributing to unwanted xenobiotic residues in milk.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104709"},"PeriodicalIF":4.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Kaidong Wang , Ge Shi , Yonghang Li , Qi Liu , Qianrong Zhang , Chenyang Wu , Yuxuan Jiao , Yuan Ma , Ai Qi , Min Huang
{"title":"Construction of a toxicity pathway from activation of the TLR4/NF-κB/NLRP3 axis to Parkinson's disease-like non-motor symptoms in mice","authors":"Kaidong Wang , Ge Shi , Yonghang Li , Qi Liu , Qianrong Zhang , Chenyang Wu , Yuxuan Jiao , Yuan Ma , Ai Qi , Min Huang","doi":"10.1016/j.etap.2025.104706","DOIUrl":"10.1016/j.etap.2025.104706","url":null,"abstract":"<div><div>Bipyridyl herbicides, like paraquat, are among the most widely used herbicides worldwide. Although the lungs are the main target organ for acute exposure to paraquat, chronic exposure to paraquat is thought to induce neurotoxicity and is one of the environmental risk factors for neurodegenerative diseases. In the last two decades, as paraquat has been banned in some regions, diquat has gradually become its replacement. However, systematic studies of environmental factor-induced neurodegenerative diseases are incomplete, and information on threats and risk assessment is still insufficient. The aim of this study was to investigate the association between bipyridine herbicides and sporadic Parkinson's disease. Among them, we refer to the concept of Adverse Outcome Pathway (AOP), integrate, analyse and propose the toxicity pathway similar to AOP. It provides ideas for us to conduct traditional toxicological studies. As a result, the present study reveals that bipyridine herbicide exposure causes neuronal pyrocytosis in locus coeruleus through activation of the TLR4/NF-κB/NLRP3 axis, resulting in the development of Parkinson's disease-like non-motor symptoms in mice.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104706"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Adrián Bullón-Téllez , Zoraida Sosa-Ferrera , José Juan Santana-Rodríguez , Natalia Garcia-Álvarez , Jesús De la Fuente , Manuel Arbelo , Antonio Fernández , Pedro López-Suárez , Carolina Oujo , Katia Freire-Lopes , Rayco Guedes-Alonso
{"title":"Environmental assessment of steroid endocrine disruptors in stranded cetaceans: A methodological approach to detection and analysis","authors":"Adrián Bullón-Téllez , Zoraida Sosa-Ferrera , José Juan Santana-Rodríguez , Natalia Garcia-Álvarez , Jesús De la Fuente , Manuel Arbelo , Antonio Fernández , Pedro López-Suárez , Carolina Oujo , Katia Freire-Lopes , Rayco Guedes-Alonso","doi":"10.1016/j.etap.2025.104703","DOIUrl":"10.1016/j.etap.2025.104703","url":null,"abstract":"<div><div>Exploring the presence of endocrine disrupting compounds in marine organisms, particularly cetaceans, is crucial to evaluate contamination within the ocean's food web and the detection of synthetic hormones in cetaceans is a strong indication of anthropogenic pollution in marine ecosystems. Due to their characteristics, blubber samples are a key component in assessing the analysis of cetaceans, but this type of sample require precise and sensitive analytical methods. Despite some methodologies have been developed for the analysis of natural steroid hormones in cetacean blubber, a significant gap persists in the comprehensive analysis of synthetic steroids within these samples. In this work, a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) extraction combined with UHPLC-MS/MS (ultra-high-performance liquid chromatography with tandem mass spectrometry) analysis was performed to determine six synthetic steroid hormones (nandrolone, prednisolone, prednisone, megestrol acetate, norethisterone, and norgestrel) in 11 stranded cetacean blubber samples. Despite the complex nature of blubber samples, the developed methodology showed promising results, with recoveries ranging from 70 % to 120 % for most target compounds at low concentration levels (150 ng·g<sup>−1</sup>). The method demonstrated high precision with relative standard deviations under 20 % in both intra- and inter-day experiments. Regarding the matrix effect, ion suppressions of about 50 % were also calculated for those samples spiked at concentration levels of 150 ng·g<sup>−1</sup>, nevertheless, all compounds were still able to be detected, in most cases below quantification limits. Notably, one sample presented a quantified concentration of megestrol acetate, a steroid hormone used in contraceptives and cancer treatments, at 26.98 ± 2.62 ng·g<sup>−1</sup>. The results affirm the methodology's effectiveness for analyzing synthetic steroid hormone levels in cetacean blubber, providing a valuable tool for assessing environmental concentrations of these anthropogenic endocrine disruptors and their impact on cetacean welfare and conservation.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104703"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Han Li , Wangjiang Feng , Tong An, Pingli Dai, Yong-Jun Liu
{"title":"Polystyrene microplastics reduce honeybee survival by disrupting gut microbiota and metabolism","authors":"Han Li , Wangjiang Feng , Tong An, Pingli Dai, Yong-Jun Liu","doi":"10.1016/j.etap.2025.104704","DOIUrl":"10.1016/j.etap.2025.104704","url":null,"abstract":"<div><div>Polystyrene microplastics (PS-MPs) pose significant risks to honeybee health. However, how microplastics (MPs) adversely influence honeybee survival through the gut pathway, especially the metabolic processes, remains poorly understood. To conduct the experiment, the honeybees (<em>Apis mellifera</em> L.) were exposed to PS-MPs (0.5 μm and 5 μm) at environmental concentrations of 25 mg/L and 50 mg/L for 21 days. Results revealed that PS-MPs reduced honeybee survival rates and food consumption. The accumulation of PS-MPs in honeybee guts caused structural damage to gut walls and elevated oxidative stress levels. Additionally, PS-MPs altered gut microbial communities, with a decrease in <em>Lactobacillus</em> and an increase in <em>Bartonella</em>. Gut metabolomics analysis indicated that PS-MPs disrupted metabolic pathways, upregulated amino acid and carbohydrate metabolism, and downregulated alpha-linolenic acid and lipid metabolism. Our study offers important insights into the physiological effects of accumulated MPs on honeybees, highlighting the critical need for effective strategies to manage environmental pollutants.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104704"},"PeriodicalIF":4.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Romina Penalba , Juan Manuel Gamez , Nancy Cardoso , Rodrigo M. Bilbao , Osvaldo J. Ponzo , Roxana Reynoso
{"title":"Effect of Bisphenol A on the neuro-immune-endocrine mechanisms controlling the reproductive axis response during an inflammatory event","authors":"Romina Penalba , Juan Manuel Gamez , Nancy Cardoso , Rodrigo M. Bilbao , Osvaldo J. Ponzo , Roxana Reynoso","doi":"10.1016/j.etap.2025.104702","DOIUrl":"10.1016/j.etap.2025.104702","url":null,"abstract":"<div><div>Endotoxin-induced toxicity could increase with previous exposure to sensitizing agents like endocrine disruptors (EDs). We studied the effects on the reproductive axis on adult male rat pups exposed to BPA since gestation day (GD) 1 to final lactation and its response to LPS before sacrifice. The decrease in GnRH release caused by LPS and BPA was more pronounced in the BPA + LPS group compared to the LPS-only group. While LPS increased nitrate production, the addition of BPA lowered it compared to both the control and LPS groups. A reduction in plasma LH levels was observed in the control, BPA + LPS, and LPS groups. Plasma testosterone decreased in the LPS, BPA, and BPA + LPS groups compared to the control, and in the BPA + LPS group compared to the LPS group. In conclusion, BPA disrupts the reproductive function and sensitizes it to LPS-induced toxicity.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104702"},"PeriodicalIF":4.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Gulminyam Baratzhanova , Hanan EL Sheikh Saad , Agnès Fournier , Marion Huguet , Olivier Joubert , Arnaud Paul , Leyla Djansugurova , Céline Cakir-Kiefer
{"title":"Comparison of the impact of chlordecone and its metabolite chlordecol on genes involved in pesticide metabolism in HepG2 cell line","authors":"Gulminyam Baratzhanova , Hanan EL Sheikh Saad , Agnès Fournier , Marion Huguet , Olivier Joubert , Arnaud Paul , Leyla Djansugurova , Céline Cakir-Kiefer","doi":"10.1016/j.etap.2025.104701","DOIUrl":"10.1016/j.etap.2025.104701","url":null,"abstract":"<div><div>Chlordecone (CLD) is an organochlorine pesticide that is highly resistant in the environment. This compound and its metabolite chlordecol (CLD-OH) still can be found in the French West Indies, after being banned 30 years ago. The novelty of this work lies in evaluating the toxicity of CLD-OH compared to CLD and examining the effects of these compounds on nuclear receptor (<em>PXR</em>, <em>PPARα</em>, and <em>CAR</em>) and metabolism-related genes (<em>CYP2B6</em>, <em>CYP3A4</em>) <em>in vitro</em> using HepG2 cell line as a model. Our study demonstrates that both compounds displayed an almost similar pattern of decrease in cell viability. Moreover, it was shown that CLD-OH can increase the expression of <em>PXR</em>, <em>CYP3A4</em>, and <em>PPARα</em> genes in comparison to CLD. The <em>AKR1C4</em> gene showed a slight decrease in expression after CLD treatment. Collectively, this study provided a new finding into the impact of CLD-OH and compares the mode of action of CLD and its metabolite<em>.</em></div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104701"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Raul A. Salazar-González , James T.F. Wise , Mark A. Doll, David W. Hein
{"title":"Metabolism and genotoxicity of 4,4’-oxydianiline is dependent on N-acetyltransferase 2 genetic polymorphism","authors":"Raul A. Salazar-González , James T.F. Wise , Mark A. Doll, David W. Hein","doi":"10.1016/j.etap.2025.104699","DOIUrl":"10.1016/j.etap.2025.104699","url":null,"abstract":"<div><div>4,4’-oxydianiline (ODA) is an environmental aromatic amine reasonably anticipated to be a human carcinogen. We investigated ODA genotoxicity and oxidative stress modified by N-acetyltransferase 2 (NAT2) genetic polymorphism in yeast and DNA repair deficient (UV5) Chinese hamster ovary cells (CHO) expressing human <em>NAT2*4</em> (rapid acetylator allele) or human <em>NAT2*5B</em> (slow acetylator allele) and in cryopreserved human hepatocytes from rapid, intermediate, or slow NAT2 acetylator genotypes. <em>N</em>-acetylation of ODA was both concentration- and time-dependent and significantly higher in yeast and CHO cells expressing <em>NAT2*4</em> versus <em>NAT2*5B</em>. ODA-induced DNA damage response and reactive oxygen species (ROS/RNS) were significantly higher, while intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) ratio or mitochondrial integrity were significantly lower in CHO cells expressing <em>NAT2*4</em> than <em>NAT2*5B</em>. Dose- and NAT2 phenotype-dependent responses also were observed in human cryopreserved human hepatocytes. Our findings have important implications for precise risk assessments following exposures to ODA and azo dye precursors.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104699"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Cong Bao , Antoine Karengera , Jan Kammenga , Inez Dinkla , Willemien Wieland , AlberTinka J. Murk
{"title":"Early life developmental effects induced by dioxins and PCBs in novel bioassays with C. elegans","authors":"Cong Bao , Antoine Karengera , Jan Kammenga , Inez Dinkla , Willemien Wieland , AlberTinka J. Murk","doi":"10.1016/j.etap.2025.104697","DOIUrl":"10.1016/j.etap.2025.104697","url":null,"abstract":"<div><div>This study assessed the effects of TCDD, two PCB mixtures (Clophen A50 and Aroclor 1254), and field extracts from marine sediments and swimming crab tissues on early-life development in Caenorhabditis elegans. Gravid nematodes were exposed on agar, and isolated eggs and larvae were tested in solution. Larval development was evaluated after 72 hours. Reporter gene assays (DR-CALUX) were also used to quantify dioxin-equivalent toxicity (TEQ). Exposure to 10 pM Clophen A50 and TCDD on agar inhibited L3–L4 transition by 60 % and 50 %, respectively. Liquid exposure to 5 µM Aroclor 1254 or TCDD (10 nM and 10 µM) delayed development by 20–40 %. Field extracts contained TEQ values of 0.67–4.91 ng/kg (0.2–1.47 pM TCDD), reducing L3–L4 development by 40–60 %. Both bioassays effectively assessed the toxicity of persistent organic pollutants in environmental samples. Agar exposure mimics realistic uptake, while liquid assays offer faster, high-throughput screening.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104697"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Deicy C. Munoz Agudelo , Hannah Whitehead , Laura L. Figueroa , Lynn S. Adler
{"title":"Pesticide residues in honey: Agricultural landscapes and commercial wax foundation sheets as potential routes of chronic exposure for honey bees","authors":"Deicy C. Munoz Agudelo , Hannah Whitehead , Laura L. Figueroa , Lynn S. Adler","doi":"10.1016/j.etap.2025.104700","DOIUrl":"10.1016/j.etap.2025.104700","url":null,"abstract":"<div><div>Pesticides pose significant threats to pollinators, and honey bees are frequently exposed through foraging and beekeeping practices. We assessed honey bee pesticide exposure by analyzing 92 pesticide residues in honey from 30 hobbyist apiaries across Massachusetts, along with store-bought honey and commercial wax foundation. For all samples, we calculated the risk of multiresidue toxicity to honey bees and assessed the role of landscape composition in predicting pesticides in local honey. Both honey and wax contained multiple pesticides, particularly neonicotinoids and piperonyl butoxide. Store-bought honey accumulated at least two times more residues than local, but did not differ significantly in toxicity. Overall, honey toxicity levels remained below thresholds of concern for bees and human consumption. Although our study had low agricultural land (∼6 %), croplands were positively correlated with pesticides in honey, while wetlands (∼ 15 %) were negatively correlated. Additionally, our study suggests that commercial wax exacerbates pesticide exposure.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"116 ","pages":"Article 104700"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}