Frontiers in toxicology最新文献

{"title":"Characterization of medical device constituents and development of duration-based non-cancer threshold of toxicological concern values.","authors":"Taylor Builee, Todd A Kennedy, Valériane Levelut, Megan A Hahn, Stephen Bond, Michael K Peterson, Frances K Hsia, Alessia Stornetta, Kristin J Erickson, Kimberly D Ehman, Bindu Prabhakar, Bradford D Bagley, Sherry P Parker","doi":"10.3389/ftox.2025.1600127","DOIUrl":"https://doi.org/10.3389/ftox.2025.1600127","url":null,"abstract":"<p><strong>Introduction: </strong>In the absence of sufficient constituent-specific dose-response toxicity data, threshold of toxicological concern (TTC) values are commonly used in toxicological risk assessment of medical device (MD) constituents. When experimental data or predictions suggest that a constituent is not likely to have genotoxic effects, categorizing the constituent into its appropriate Cramer Class and application of the corresponding TTC value is recommended. This paper presents the uniqueness of the MD chemical space when compared to the historical Munro TTC dataset via structure-based chemical taxonomy, ToxPrint chemotypes, physicochemical properties and molecular descriptors, and proposes duration-based MD non-cancer TTC values.</p><p><strong>Methods: </strong>More than 15,000 MD constituents were identified and screened, and 790 constituents met the established criteria for inclusion. Constituents with chemotypes matching inorganic substances, metals, pharmacologically active, nitroso-like, aflatoxin-like, azoxy, benzidine, polyhalogenated dibenzodioxins, dibenzofurans, biphenyls, high molecular weight polymers, nanomaterials, proteins, and radioactive substances were excluded from the evaluation. Constituent-specific toxicity data were obtained from the data-rich and open-access, European Chemicals Agency Registration, Evaluation, Authorisation and Restriction of Chemicals (ECHA REACH) database. Considered protective for systemic, developmental, and reproductive toxicity, constituent-specific oral no-observed-adverse-effect-level (NOAEL) values from repeated dose studies with a reliability (Klimisch) score of 1 or 2 were selected as the point of departure (POD) for each duration (subacute/subchronic/chronic/lifetime). The NOAEL values selected as PODs for each constituent in each duration category were plotted using log-normally fitted cumulative frequency distributions, and an uncertainty factor of 100 (10 each for inter and intraspecies differences) was applied to the lowest fifth percentile NOAEL value extrapolated from each curve.</p><p><strong>Results: </strong>The resulting non-cancer TTC values for various exposure duration categories were 112 μg/kg/day for ≤ 1 day to 30 days, 111 μg/kg/day for 31 to 365 days and 41 μg/kg/day for ≥ 366 days.</p><p><strong>Discussion: </strong>The proposed MD non-cancer TTC values followed the same approach as derivation of the Munro TTC values; however, they are derived exclusively from MD constituents with chemical-specific data for the appropriate period of assumed exposure to the constituent.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1600127"},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327908","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 effects of nanoplastics on fish.","authors":"Asok K Dasmahapatra, Joydeep Chatterjee, Paul B Tchounwou","doi":"10.3389/ftox.2025.1530209","DOIUrl":"10.3389/ftox.2025.1530209","url":null,"abstract":"<p><p>The global concern about plastics has been amplified due to their widespread contamination in the environment and their ability to cross biological barriers in living organisms. However, our understanding of their bioaccumulation, toxicity, and interaction with other environmental pollutants remains limited. Plastics are classified into three categories: macro-(MAP > 5 mm), micro-(MIP, <5 mm), and nanoplastics (NAP≤ 100 nm). Among these, NAPs have superior sorption capacity, a large surface area, and a greater ability to release co-contaminants into tissues, resulting in more complex and harmful effects compared to MAPs and MIPs. To assess the toxic effects of NAPs, particularly their genotoxicity in fish, we carried out a bibliographic search in PubMed using the search terms \"nanoplastics\" and \"fish,\" which yielded 233 articles. These studies focused on various polymers including polyamide (PA), polycarbonate (PC), polyethylene (PE), polyethylene terephthalate (PET), polymethylmethacrylate (PMMA), polypropylene (PPP), polystyrene (PS), and polyvinyl chloride (PVC). We further refined our search by including fish species such as common carp, fathead minnows, medaka, tilapia, trout, and zebrafish and selected 114 articles for review. This article provides a comprehensive overview of the current state of knowledge on the effects of NAPs on fishes, emphasizing their interaction with co-contaminants including metals, polycyclic aromatic hydrocarbons, pharmaceuticals, pesticides, antibiotics, plastic additives, and endocrine disruptors found in the aquatic environments. Our findings indicate that among fish species, zebrafish (∼68%) is the most frequently studied, while PS (∼89%) is the most commonly encountered NAP in the aquatic ecosystems. Despite substantial experimental variability, our systematic review highlights that NAPs accumulate in various tissues of fish including the skin, muscle, gill, gut, liver, heart, gonads, and brain across all developmental stages, from embryos to adults. NAP exposure leads to significant adverse effects including increased oxidative stress, decreased locomotor and foraging activities, altered growth, immunity, lipid metabolism, and induced neurotoxicity. Furthermore, NAP exposure modulates estrogen-androgen-thyroid-steroidogenesis (EATS) pathways and shows potential intergenerational effects. Although the USEPA and EU are aware of the global impacts of plastic pollution, the prolonged persistence of plastics continues to pose a significant risk to both aquatic life and human health.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1530209"},"PeriodicalIF":3.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303841","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":"Repetitive ozone exposure worsens features of muco-inflammatory disease in developed <i>Scnn1b</i>-Tg+ mice lungs.","authors":"Thao Vo, Sonika Patial, Yogesh Saini","doi":"10.3389/ftox.2025.1540468","DOIUrl":"10.3389/ftox.2025.1540468","url":null,"abstract":"<p><strong>Introduction: </strong>Ambient exposure to ozone (O₃), one of the six criteria pollutants, is associated with the exacerbation of respiratory symptoms in individuals with underlying lung diseases. Using <i>Scnn1b</i>-Tg+ (Tg+) mice, a widely used model of muco-inflammatory lung disease, we have demonstrated that O₃ exposure during the early stages of postnatal lung development leads to exacerbated muco-inflammatory outcomes. However, it remains unclear whether O₃ affects the developed lungs differently than the underdeveloped lungs of Tg+ mice.</p><p><strong>Methods: </strong>We exposed 3-week-old wild-type (WT) and Tg+ mice to either filtered air (FA) or 0.8 ppm O₃ for 3 weeks and examined the lung phenotypes 12-16 h post-last exposure.</p><p><strong>Results: </strong>As compared to FA-exposed WT mice, O₃-exposed WT mice showed increased bronchoalveolar lavage fluid (BALF) proteins, increased immune cells, increased inflammation, alveolar space enlargement, and tissue consolidation. As compared to FA-exposed WT mice, the FA-exposed Tg+ mice showed increased immune cells, elevated levels of inflammatory mediators, e.g., IL-5, G-CSF, MIP-2, KC, MIP-1α, MIP-1β, IP-10, TNF-α, and IL-17, increased inflammation, alveolar space enlargement, tissue consolidation. As compared to FA-exposed <i>Scnn1b</i>-Tg+ mice, O₃-exposed Tg+ mice had increased total protein, total dsDNA, and phagocytosed lipid contents, in addition to exaggerated granulocytic recruitment, peripheral and bronchiolar inflammation, alveolar space enlargement, and tissue consolidation.</p><p><strong>Discussion: </strong>Together, our data using Tg+ mice with developed lungs exhibited several findings consistent with previous findings observed in Tg+ neonates. Interestingly, however, as opposed to the previous report in O₃-exposed neonatal Tg+ mice, where the hallmark features of Tg+ airway disease, i.e., mucus obstruction and expression of major gel-forming mucins (MUC5B and MUC5AC) were found exacerbated by O₃ exposure, the FA- and O₃-exposed Tg+ mice with developed lungs exhibited comparable responses. These differential responses suggest that the stage of lung development is an important factor in the modulation of epithelial remodeling following O₃ exposure.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1540468"},"PeriodicalIF":3.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268032","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":"Immunotoxicity assessment of multiwalled carbon nanotubes following whole-body inhalation exposure for 30 and 90 days in B6C3F1/N mice and 30 days in HSD:Harlan Sprague Dawley SD^® rats.","authors":"Victor J Johnson, Nigel J Walker, Michael I Luster, Gary R Burleson, Michelle Cora, Gregory L Baker, Barney Sparrow, Dori R Germolec","doi":"10.3389/ftox.2025.1539810","DOIUrl":"10.3389/ftox.2025.1539810","url":null,"abstract":"<p><strong>Background: </strong>Several lines of evidence suggest the possibility that inhalation exposure to multi-walled carbon nanotubes (MWCNT) at occupationally relevant doses can lead to systemic immunotoxicity. To test this hypothesis, we undertook in-depth examination of immune function in mice and rats exposed by inhalation to relatively low levels of 1020 Long Multiwalled Carbon Nanotubes (L-MWNT-1020).</p><p><strong>Methods: </strong>Studies were conducted to determine the systemic and pulmonary immunotoxic effects in mice and rats exposed to L-MWNT-1020 following whole-body inhalation for 6 h/day for 5 days/week for 30 (mice and rats) and 90 (mice) days at dose levels of 0, 0.06, 0.2, and 0.6 mg/m³. Additional groups were administered cyclophosphamide (CPS) as a positive control for each cohort. Following exposure, pulmonary macrophage phagocytosis, immunophenotypic analysis of immune cells populations in the spleen, and systemic immune function, including tests for humoral (T-dependent antibody response, TDAR), cell-mediated (cytotoxic T-lymphocyte [CTL] activity), and innate (Natural Killer [NK] cell activity) immunity were conducted.</p><p><strong>Results: </strong>While exposure increased pulmonary macrophage activity, no major changes were observed in any of the systemic immune parameters measured in mice exposed for 30 or 90 days. In rats, there was a slight decrease in humoral immunity coinciding with an increase in the number of splenic T cell and NK cell populations.</p><p><strong>Conclusion: </strong>Although pulmonary macrophage activity increased in mice following exposure to L-MWNT-1020, systemic immune function for the most part remained unaffected. In contrast, rats demonstrated a slight decrease in humoral immune function as well as an increase in spleen cell numbers, T cell, and NK cell populations suggesting species-specific effects on systemic immunity, however, these effects were small and their biological significance with respect to altering disease susceptibility is unclear.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1539810"},"PeriodicalIF":3.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259530","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":"Residential proximity to agricultural fields, urinary glyphosate levels and breast cancer risk: a case-control study in Argentina.","authors":"Florencia Doná, Virginia Lorenz, Georgina Stegmayer, Tamara Ricardo, Stefanía D'Iorio, Fernando Ponzo, María Rosa Repetti, Luisina Delma Demonte, María Mercedes Milesi, Jorgelina Varayoud","doi":"10.3389/ftox.2025.1579952","DOIUrl":"10.3389/ftox.2025.1579952","url":null,"abstract":"<p><p>Despite accumulated evidence indicating glyphosate herbicide (GLY) presents endocrine disrupting properties, there are still discrepancies. Moreover, few epidemiological studies have focused on hormone-related pathologies. This work aimed to investigate the associations between urinary GLY levels and breast cancer (BC) in women from a region of intense agricultural activity in Argentina, exploring residential proximity to agricultural fields as a potential risk factor for BC. This was a case-control study that involved 90 women from different populations in the Province of Santa Fe, Argentina. Demographic data, lifestyle factors, and residential history were obtained through a questionnaire, while medical outcomes and reproductive history were acquired from medical records. Spot urine samples were collected and the concentrations of GLY and its primary metabolite, aminomethylphosphonic acid (AMPA) were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Odds ratios were estimated to assess the strength of the association between the case/control type and each predictor. GLY concentrations were above the limit of detection (LOD) in 86.1% of samples, with a range of 0.37-10.07 µg GLY/g creatinine. AMPA was not detected in any of the samples analyzed. Although urinary GLY concentrations showed no differences between the case and control groups, women residing near agricultural fields showed an increased risk of BC (OR: 7.38, 95% CI: 2.74-21.90). These original findings show the ubiquitous presence of GLY in adult women from Argentina. Interestingly, women living near agricultural fields have a higher risk of BC, suggesting that exposure not only to GLY but also to agrochemicals in general, could predispose to the development of BC in Argentina. While this study provides valuable insights, further and broader assessments of BC distribution in relation to agrochemical exposure acroos different regions of Argentina are needed.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1579952"},"PeriodicalIF":3.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227867","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":"Quantitative adverse outcome pathway modeling for cigarette smoke-inducible airway mucus hypersecretion. Part 2: Bayesian network modeling for probabilistic risk estimation.","authors":"Shigeaki Ito, Sakuya Ichikawa, Risa Matsumoto, Shugo Muratani, Keigo Sano, Akina Mori, Kazuo Erami","doi":"10.3389/ftox.2025.1564864","DOIUrl":"10.3389/ftox.2025.1564864","url":null,"abstract":"<p><p>The development of <i>in vitro</i> tests that reproduce real-world situations is crucial for toxicity- and disease-risk assessment without animal testing. Because signs and symptoms of health concerns can be complex, it is helpful to create a simplified representation of such manifestations using a conceptual framework such as an adverse outcome pathway (AOP). Combining an AOP with computational models could be a potential tool for the extrapolation of <i>in vitro</i> results to real-world scenarios. Here, we applied Bayesian network-based probabilistic quantitative models for disease-related risk estimation using an <i>in vitro</i> dataset on the AOP of mucus hypersecretion-a known representative symptom of chronic airway disease-obtained by repeated exposure of human bronchial epithelial cells to whole cigarette smoke. We also used a computational aerosol dosimetry model to account for differences between <i>in vitro</i> exposure concentrations and human exposure scenarios. The results revealed dose- and exposure repetition-dependent increases in adverse outcome probability, suggesting that the model reflects the risk continuum of cigarette smoking. Furthermore, under certain assumptions, dosimetry modeling indicated that our <i>in vitro</i> exposure concentrations were similar to actual smoking scenarios. As an exercise, we also calculated <i>in vitro</i> odds ratios for chronic bronchitis that were comparable to the range of real-world odds ratios for chronic bronchitis due to cigarette smoking. Our combinatory risk-assessment approach could be a valuable tool for estimating the chronic inhalation effects of inhalable products and chemicals.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1564864"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182198","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":"Quantitative adverse outcome pathway modeling for cigarette-smoke-induced airway mucus hypersecretion. Part 1: adverse-outcome-pathway-based <i>in vitro</i> assessment with repeated exposure to whole cigarette smoke.","authors":"Sakuya Ichikawa, Shugo Muratani, Keigo Sano, Kazuo Erami, Akina Mori, Risa Matsumoto, Shigeaki Ito","doi":"10.3389/ftox.2025.1564857","DOIUrl":"10.3389/ftox.2025.1564857","url":null,"abstract":"<p><p>Adverse outcome pathway (AOP)-based chemical risk assessment is a promising tool for regulatory decision-making and is typically used in toxicological assessments. However, it also holds potential for pharmacological and disease-related evaluations. The present study focuses on an AOP for decreased lung function. Lung function is normally robustly maintained by homeostatic capacity, but repeated and chronic stimulation can disrupt this capacity, leading to impaired lung function and mucus hypersecretion. We developed an AOP-based <i>in vitro</i> method to test the disease-related states that can be reproduced by exposing three-dimensionally cultured human bronchial epithelial cells (3D-HBECs) to whole cigarette smoke (WCS). Over a duration of 2 weeks, we repeatedly exposed 3D-HBECs from six different donors to WCS six times to observe both acute phase responses (oxidative stress, epidermal growth factor receptor activation, and SP1 activation) and chronic phase responses (intracellular mucus production, goblet cell metaplasia/hyperplasia, and mucus hypersecretion) along the AOP. Our results demonstrate that although the repeated exposure to WCS induced biological responses along the AOP in all donors, there were interdonor differences, particularly in the timing and amplitudes of the chronic phase responses. All smokers do not exhibit phenotypic changes with the same smoking duration, so this variability likely reflects individual differences. We anticipate that our AOP-based assessment method combined with computational quantitative AOP modeling (discussed in Part 2) will become a valuable tool for assessing the disease risk of airborne materials and inhalable products.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1564857"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180619","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":"Editorial: Legacy & emerging contaminants in the aquatic environment-bridging knowledge, policy, and future.","authors":"Abdul Qadeer, Mengyang Liu, Sanjeeb Mohapatra, Racliffe Weng Seng Lai","doi":"10.3389/ftox.2025.1611852","DOIUrl":"10.3389/ftox.2025.1611852","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1611852"},"PeriodicalIF":3.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183446","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":"Optimizing Wnt activation in fetal calf serum (FCS)-free organoid expansion media.","authors":"Esther J M Liefting, Jeffrey J Bajramovic","doi":"10.3389/ftox.2025.1504469","DOIUrl":"10.3389/ftox.2025.1504469","url":null,"abstract":"<p><p>Organoid technology can revolutionize biomedical research by increasing the translational value of experimental results while at the same time reducing the need for experimental animal use. However, in most cases the organoid culture workflow relies on expansion media that contain fetal calf serum (FCS). The production of FCS causes animal suffering, and the use of it is hampered by factors that negatively impact the reproducibility (such as the large inter-batch variation and the undefined composition of FCS), relevance (such as the induction of a non-physiological cellular phenotype), as well as the clinical translatability (such as the potential to cause xeno-immunization or to contain xenogeneic pathogens). There is thus a strong impetus to find animal-free alternatives to the use of FCS. Most contemporary expansion media for organoid culture are not FCS-free. This is mainly contributable to the use of FCS for the recombinant production of the growth factor Wnt3A. Wnt3A-conditioned medium is added to expansion media to induce Wnt signaling, which is necessary for organoid proliferation. In turn, FCS is pivotal to stabilize and solubilize the Wnt3A protein, and not perse for the survival, adhesion or proliferation of cells. This mini-review explores alternative methods to induce Wnt signaling in organoid expansion media, encompassing the use of soluble Wnt mimetics, the use of carriers, and the use of small molecule inhibitors. Ultimately, alternative Wnt activation approaches for different experimental goals are reviewed and discussed.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1504469"},"PeriodicalIF":3.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176005","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":"Case report: Treatment of severe phorate poisoning.","authors":"Wang Kunlun, Yuan Jun, Xu Shiming, Shen Jie, Gao Mingqiang, Zhang Yuxia, Mo Weichun","doi":"10.3389/ftox.2025.1581362","DOIUrl":"10.3389/ftox.2025.1581362","url":null,"abstract":"<p><strong>Background: </strong>Phorate is a highly toxic organophosphorus pesticide. Owing to its low cost and insecticidal potency, it is still widely used in parts of China, resulting in cases of occupational and life poisoning. This article presents the treatment process for phorate poisoning and monitoring the toxic metabolites terminology in the body.</p><p><strong>Case report: </strong>A 23-year-old male patient ingested about 300 mL (180 g) of 60% phorate emulsion 4 h before admission at our hospital. The patient had ingested over 300 times the lethal dose. During hospitalization, the patient's levels of cholinesterase, phorate and its metabolites, atropine and pralidoxime chloride (PAM), were monitored. Phorate was quickly absorbed into the blood, producing five metabolites. Before hemoperfusion (HP), the concentration of phorate in the blood could not be detected. After the first HP we found five metabolites of phorate in the blood (phoratoxon sulfoxide,phoratoxon sulfone, phorate sulfone, phorate sulfoxide, and phoratoxon). In the follow-up treatment, the concentration of five metabolites gradually decreased. The concentration of the phorate sulfoxide and phorate sulfone rebounded with the suspension of HP, but that of the other metabolites did not rebound. It took 20 days for cholinesterase to recover. Treatment included multiple rounds of HP, atropinization, and reactivator of cholinesterase by PAM. The patient recovered after 34 days and was discharged from hospital.</p><p><strong>Conclusion: </strong>Phorate is oxidized and catalyzed into five metabolites, which cause the toxic effects. Phoratoxon sulfoxide has the highest concentration of these metabolites, followed by phoratoxon sulfone, phorate sulfone, phorate sulfoxide, and phoratoxon, respectively. HP treatment significantly lowered the serum levels of the toxic metabolites terminology. If HP treatment is interrupted, the serum levels of phorate sulfoxide and phorate sulfone tend to rise again. It takes a long time for cholinesterase to recover from severe phorate poisoning.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1581362"},"PeriodicalIF":3.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144777","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}