Frontiers in toxicologyPub Date : 2025-06-30eCollection Date: 2025-01-01DOI: 10.3389/ftox.2025.1602065
Iris Mueller, Ashraf Abdelkhaliq, Paul Carmichael, Matthew Dent, Marleen Feliksik, Luke Flatt, Jade Houghton, José M Horcas Nieto, Amer Jamalpoor, Predrag Kukic, Sophie Malcomber, Beate Nicol, Gopal Pawar, Claire Peart, Katarzyna Przybylak, Magdalena Sawicka, Katy Wilson, Kathryn Wolton
{"title":"An advancement in developmental and reproductive toxicity (DART) risk assessment: evaluation of a bioactivity and exposure-based NAM toolbox.","authors":"Iris Mueller, Ashraf Abdelkhaliq, Paul Carmichael, Matthew Dent, Marleen Feliksik, Luke Flatt, Jade Houghton, José M Horcas Nieto, Amer Jamalpoor, Predrag Kukic, Sophie Malcomber, Beate Nicol, Gopal Pawar, Claire Peart, Katarzyna Przybylak, Magdalena Sawicka, Katy Wilson, Kathryn Wolton","doi":"10.3389/ftox.2025.1602065","DOIUrl":"10.3389/ftox.2025.1602065","url":null,"abstract":"<p><p>Traditional chemical safety assessment involves identifying the lowest level of a chemical that impacts endpoints measured in standardized animal studies to establish human exposure limits. <i>In vitro</i> assays have shown promise in providing points of departure that can be protective of human health when combined with exposure predictions into a bioactivity:exposure ratio (BER). Using a combination of broad screening tools and DART-targeted assays, we previously demonstrated high biological coverage of this NAM toolbox against a list of DART-relevant genes and pathways. To fully transition to an animal-free paradigm, it is crucial to establish confidence that these <i>in vitro</i> assays sufficiently represent the DART toxicity mechanisms, ensuring a level of protection that is safe for non-pregnant adults, pregnant women, and fetal populations. In this proof-of-concept study, we have extended the toolbox to include additional <i>in vitro</i> and <i>in silico</i> tools and have performed an evaluation using 37 benchmark compounds across 49 exposure scenarios. According to existing regulatory opinions, 18 of these scenarios would be considered high-risk chemical exposures from a DART perspective. Our DART NAM toolbox approach identified 17 out of these 18 high-risk scenarios. We further investigated the impact of population-based changes in pregnancy and the fetus on internal exposures by evaluating human clinical data where available for the 37 compounds. In most instances, the variability resulting from pregnancy or gestational changes falls within the range of toxicokinetic variability observed in the general population. This work demonstrates that protective safety decisions can be made for DART without generating new animal test data.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1602065"},"PeriodicalIF":3.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638785","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}
Frontiers in toxicologyPub Date : 2025-06-30eCollection Date: 2025-01-01DOI: 10.3389/ftox.2025.1554747
Patrudu Makena, Linsey E Haswell, Michael McEwan, Brian M Keyser, David E Smart, Robert Leverette, Kristen Jordan, Damien Breheny, Sarah Baxter-Wright
{"title":"An adverse outcome pathway for cigarette smoke-mediated oxidative stress in plaque formation.","authors":"Patrudu Makena, Linsey E Haswell, Michael McEwan, Brian M Keyser, David E Smart, Robert Leverette, Kristen Jordan, Damien Breheny, Sarah Baxter-Wright","doi":"10.3389/ftox.2025.1554747","DOIUrl":"10.3389/ftox.2025.1554747","url":null,"abstract":"<p><p>Adverse outcome pathways (AOPs) have been developed as a risk assessment tool for regulatory applications. These AOPs describe a logical mechanistic sequence of events, starting with a Molecular Initiating Event (MIE), and ultimately leading to a disease outcome via a series of Key Events (KE). The AOP framework provides a system to make predictions and assessments while reducing the need for <i>in vivo</i> assessment. In the absence of epidemiological evidence, assessment of the health effects of a product, chemical or therapy on the progression of atherosclerosis would necessitate long-term animal exposure studies such as the use of the Apolipoprotein E deficient mouse. We followed Organisation for Economic Co-operation and Development (OECD) guidelines to formulate and propose an AOP for atherosclerotic plaque progression, collating the evidence by which cigarette smoke-induced oxidative stress forms a MIE. The downstream pathway includes multiple KEs including the upregulation of proinflammatory mediators, nitric oxide depletion, and endothelial dysfunction. Alterations in these KEs can lead to plaque formation and progression in cardiovascular disease and increase the risk of morbidity and mortality. Identifying preclinical endpoints and clinical biomarkers associated with these KEs provides a framework for <i>in vitro</i> and clinical data, supporting a mechanistic narrative for regulatory assessment. The application of this pathway provides a powerful alternative to animal models through developing preclinical assays and biomarkers for the assessment of atherosclerosis progression risk.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1554747"},"PeriodicalIF":3.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638786","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":"Towards the standardization of human platelet lysate production and its comparison to fetal bovine serum for human hematopoietic cell culture: a scoping review.","authors":"Shamili Immalaraju, Srishti Goyal, Rukmini Jonnalagadda","doi":"10.3389/ftox.2025.1496231","DOIUrl":"10.3389/ftox.2025.1496231","url":null,"abstract":"<p><p>Human hematopoietic cell culture (HCC) refers to the <i>ex vivo</i> growth of normal cells of the hematological system. These cells can be used as models to understand hematopoiesis and related malignancies. HCC also holds immense potential to help develop safer vaccines and immunotherapies, as well as donor-independent blood products. <i>In vivo</i>, these cells grow and differentiate in highly specialized conditions but replicating these <i>in vitro</i> is a significant technical challenge. Although various strategies have been developed to optimize HCC expansion, implementing them can be costly. Consequently, traditional fetal bovine serum (FBS)-containing media is the first choice, despite its disadvantages. Over the past two decades, human platelet lysate (hPL) has emerged as a viable alternative. However, variations in protocols and reporting standards across laboratories have resulted in a mixed picture regarding its feasibility to replace FBS. Thus, this study aimed to review existing literature that directly compared HCC performance in hPL and FBS supplementation. PubMed, Google Scholar, and the FCS-free database were queried between 1 January to 30 July 2024. Using pre-defined inclusion and exclusion criteria, five out of 622 relevant records were included in this scoping review. Data on the hPL production method, HCC conditions and performance were extracted. We identified gaps in the consideration of key hPL production parameters and recommend addressing them to reduce the variability observed in hPL performance. Even though hPL production parameters were repeatedly overlooked, hPL outperformed FBS supplementation in terms of cell identity and functionality across the included HCC studies. Therefore, we highlight the potential of these recommendations to overcome existing technical challenges in HCC, as well as support the development of effective FBS alternatives by enhancing the reproducibility and reporting standards of future studies.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1496231"},"PeriodicalIF":3.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627901","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: Evaluating toxic encephalopathy from occupational 1,2-dichloroethane exposure: magnetic resonance imaging contributions.","authors":"Jieru Wang, Tianzi Jian, Guangcai Yu, Baotian Kan, Wei Li, Xiangdong Jian","doi":"10.3389/ftox.2025.1557995","DOIUrl":"10.3389/ftox.2025.1557995","url":null,"abstract":"<p><strong>Background: </strong>1,2-Dichloroethane is a commonly used industrial solvent. Acute or subacute occupational exposure can cause toxic encephalopathy; however, long-term changes in brain imaging are not frequently documented.</p><p><strong>Case presentation: </strong>A 39-year-old woman developed dizziness and forgetfulness 9 days after performing glue coating. Her symptoms improved significantly after a 7-day break from work. However, after resuming work for 3 days, she returned with dizziness, headache, and anxiety. Brain magnetic resonance imaging (MRI) showed extensive edema and diffuse abnormal signal intensities in the cerebellar dentate nucleus, basal ganglia, and bilateral cerebral white matter. She was treated with salvianolate injection, magnesium isoglycyrrhizinate, and neurotrophic therapy. Two weeks after admission, her symptoms improved significantly, except for mild uncoordinated walking. The range of abnormal MRI signals remained consistent with previous findings. She was discharged the following day. She experienced worsened headache 3 days later. Computed tomography revealed diffuse cerebral edema. Despite treatment with mannitol, her headache rapidly worsened and was accompanied by nausea, vomiting, hypertension, bradycardia, and dyspnea, ultimately leading to unconsciousness. Follow-up MRI showed findings similar to the previous scan, except that the apparent diffusion coefficient (ADC) sequence had changed from hypointense to hyperintense. Shortly after the MRI examination, she experienced respiratory arrest. Unfortunately, she died 32 days after her initial admission due to severe cerebral injury and infection.</p><p><strong>Conclusion: </strong>Occupational exposure to 1,2-dichloroethane can lead to toxic encephalopathy, presenting as diffuse progressive cerebral edema. This case shows that brain imaging findings may not always correlate with the patient's clinical condition, so careful monitoring is essential.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1557995"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602436","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}
Frontiers in toxicologyPub Date : 2025-06-25eCollection Date: 2025-01-01DOI: 10.3389/ftox.2025.1572324
Roy Gerona, Daniel Tomer, Donovan Nielsen, Allyson C Sage, Deborah French, Juliana Tolles, James Alan Chenoweth
{"title":"New psychoactive substances in roadway crash victims in California.","authors":"Roy Gerona, Daniel Tomer, Donovan Nielsen, Allyson C Sage, Deborah French, Juliana Tolles, James Alan Chenoweth","doi":"10.3389/ftox.2025.1572324","DOIUrl":"10.3389/ftox.2025.1572324","url":null,"abstract":"<p><strong>Background: </strong>Motor vehicle crashes (MVCs) are a major global health concern. While alcohol continues to be a significant contributor to MVCs, the role of illicit and prescription drugs has increased in the last 4 decades. Moreover, the proliferation of new psychoactive substances (NPS) in the United States since 2010 has reshaped recreational drug use. Despite this, its contribution to MVCs has not been systematically evaluated. In this study, we report the prevalence of NPS in roadway crash victims in California.</p><p><strong>Methods: </strong>Serum samples from 1000 roadway crash victims were collected and analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) against a comprehensive database of 1314 drugs, including 1008 NPS, and quantitative analysis was performed using isotope dilution. Alcohol was quantified in an autoanalyzer using an enzymatic method employing alcohol dehydrogenase.</p><p><strong>Results: </strong>Eight NPS (detection frequency = 26) were confirmed and quantified in 17 cases. Like current nationwide NPS surveillance studies, bromazolam, para-fluorofentanyl, and mitragynine were most frequently detected. NPS were detected in polypharmacy use, with traditional recreational drugs such as fentanyl, methamphetamine, and delta-9 THC most frequently co-detected. The serum geometric means detected for bromazolam (5.41 ng/mL; range: 0.22-26.59), para-fluorofentanyl (0.45 ng/mL; range: 0.28-2.02) and mitragynine (7.02; range: 0.55-90.55) were lower than those reported for overdose and death cases.</p><p><strong>Discussion: </strong>This study is the first to report quantitative levels of multiple NPS and multiple NPS classes in a large US roadway crash survey, with the high detection of CNS depressants and their co-occurrence with traditional recreational drugs highlighting the need for expanded NPS testing, roadside testing strategies, and guidelines for determining drug-induced impairment; the quantitative data may be valuable in establishing these guidelines.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1572324"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602437","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}
Frontiers in toxicologyPub Date : 2025-06-23eCollection Date: 2025-01-01DOI: 10.3389/ftox.2025.1585430
Peter S Walmod, Philip Kusk, Nina Jøhnk, Ieva Ankorina-Stark, Anthony Essex
{"title":"An injectable 2.5% cross-linked polyacrylamide hydrogel (2.5 iPAAG) demonstrates no neurotoxicity in human induced pluripotent stem cells-derived iCell<sup>®</sup> GlutaNeurons.","authors":"Peter S Walmod, Philip Kusk, Nina Jøhnk, Ieva Ankorina-Stark, Anthony Essex","doi":"10.3389/ftox.2025.1585430","DOIUrl":"10.3389/ftox.2025.1585430","url":null,"abstract":"<p><strong>Introduction: </strong>Arthrosamid<sup>®</sup>, Arthramid<sup>®</sup>, Bulkamid<sup>®</sup>, and Mictamid<sup>®</sup> are products for the management of osteoarthritis and female urinary incontinence. All four products include the same injectable hydrogel consisting of 2.5% crosslinked polyacrylamide termed 2.5 iPAAG that is polymerized from the neurotoxic compound acrylamide.</p><p><strong>Methods: </strong>To investigate whether 2.5 iPAAG demonstrates any neurotoxic effects <i>in vitro</i>, human iCell<sup>®</sup> Glutaneurons were exposed to concentrations of up to 20% (w/w) 2.5 iPAAG for up to 96 h. Cells were stained and recorded by fluorescence microscopy for the subsequent estimation of cell survival, cell death, apoptosis, and the formation and maintenance of the neurite network.</p><p><strong>Results: </strong>The negative control, Fish Gelatin, did not affect cell survival, cell death, or apoptosis, and had no or minor effects on the neurite network area. The positive controls acrylamide and A23187 caused a pronounced time- and dose-dependent decrease in cell survival, an increase in cell death, but not apoptotic cell death, and a strong decrease in neurite network area, whereas another positive control, Tunicamycin, caused a time- and dose-dependent increase in cell death and apoptosis but only a minor decrease in the average neurite network area. At the tested concentrations and timepoints, the 2.5 iPAAG had no statistically significant effects on cell survival, non-apoptotic and apoptotic cell death, or the neurite network area.</p><p><strong>Discussion: </strong>These results support the interpretation that 2.5 iPAAG demonstrates no apparent <i>in vitro</i> neurotoxic or cytotoxic effects in human iCell<sup>®</sup> Glutaneurons when included in cell cultures at concentrations of up to 20% (v/v) for up to 96 h.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1585430"},"PeriodicalIF":3.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585749","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}
Frontiers in toxicologyPub Date : 2025-06-12eCollection Date: 2025-01-01DOI: 10.3389/ftox.2025.1574387
Camden Holm, Joseph Finelli, Mateo Frare, Alex Armento, Seyoum Ayehunie
{"title":"Bioengineering of novel organotypic 3D human liver tissue model for drug-induced liver injury and toxicity studies.","authors":"Camden Holm, Joseph Finelli, Mateo Frare, Alex Armento, Seyoum Ayehunie","doi":"10.3389/ftox.2025.1574387","DOIUrl":"10.3389/ftox.2025.1574387","url":null,"abstract":"<p><strong>Background: </strong>In drug development, liver failure is the cause of approximately 30% of post marketing withdrawals of pharmaceuticals. Drug-induced liver injury (DILI) remains the leading cause of acute liver failure (ALF), accounting for approximately 15% of the cases.</p><p><strong>Materials and methods: </strong>In this study, we developed a novel human three-dimensional (3D) liver tissue model by seeding adult primary human hepatocytes onto cell culture inserts under Air-Liquid Interface (ALI) condition for extended culture periods. The engineered tissues were thoroughly characterized for barrier integrity using transepithelial electrical resistance (TEER) measurements and assessed for tissue morphology and structure via hematoxylin and eosin (H&E) staining and immunohistochemistry. Expression levels of drug transporters and drug-metabolizing enzymes were evaluated by quantitative PCR (qPCR). The functionality of the tissue model for drug toxicity assessment was demonstrated by comparison with conventional two-dimensional (2D) monolayer hepatocyte cultures and liver spheroids. To evaluate the model's relevance for DILI studies, we exposed the 3D liver tissues to compounds with well-documented hepatotoxic profiles in humans. Liver function was monitored by quantifying biomarkers such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) released into the culture medium.</p><p><strong>Results: </strong>The engineered 3D liver tissue model exhibited distinct apical and basolateral surfaces, reflecting a polarized and stratified architecture that closely mimics native liver tissue. Morphological and phenotypic analyses confirmed the tissue's organotypic features. Gene expression profiling revealed elevated levels of liver-specific genes involved in drug transport, metabolism, and clearance. Functionally, the tissue metabolized midazolam--a substrate of the cytochrome P450 3A4 (CYP3A4) enzyme--into its primary metabolite, 1-hydroxymidazolam. Upon repeated exposure to fialuridine, a discontinued anti-hepatitis B drug known for causing severe liver toxicity in humans, the tissue model exhibited barrier compromise, reduced albumin production, and increased levels of ALT and AST in a time- and concentration-dependent manner.</p><p><strong>Discussion: </strong>The results strongly suggest the model's physiological relevance and functionality in predicting drug responses in humans. Thus, the engineered 3D organotypic human liver tissue model which can be cultured for weeks and produced in a semi-high throughput format creates an opportunity to study drug-induced liver toxicity in an in vitro microenvironment. The reconstructed 3D liver tissue model can serve as a tool for alternative methods intended to reduce animal use in experimentation.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1574387"},"PeriodicalIF":3.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509804","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}
Frontiers in toxicologyPub Date : 2025-06-09eCollection Date: 2025-01-01DOI: 10.3389/ftox.2025.1568207
Kaelas R Munger, Killian M Anreise, Robert M Strongin
{"title":"Cannabis concentrate vaping chemistry.","authors":"Kaelas R Munger, Killian M Anreise, Robert M Strongin","doi":"10.3389/ftox.2025.1568207","DOIUrl":"10.3389/ftox.2025.1568207","url":null,"abstract":"<p><strong>Background: </strong>This review article addresses the vaping chemistry of manufactured cannabis concentrates-a topic that remains under-researched despite the widespread availability and growing popularity of these products. Given their current prevalence and the fact that many of the findings discussed herein are from early-stage investigations, further research is essential to fully assess the public health risks associated with concentrate use. The purpose of this article is to help begin to bridge this knowledge gap by outlining the technical challenges of studying cannabis concentrates and to present evidence-based data concerning toxicant exposures as a foundation for future investigations.</p><p><strong>Methods: </strong>A search of cannabis concentrate vaping within the date range of 2019-2025 on Google Scholar returned approximately 2,700 hits. A cannabis concentrate was defined as a sample containing at least 50% (w/w) cannabinoids. In addition to our group's articles, the search results contained six manuscripts that described at least a partial focus on molecular emissions specifically derived from vaping or dabbing samples that included cannabis concentrates.</p><p><strong>Findings: </strong>Studying cannabis concentrate vaping poses distinct technical challenges that differ from those associated with electronic nicotine delivery systems. Emissions from vaping concentrates contain a substantial proportion of harmful aerosol toxicants, including isoprene, 3-methylcrotonaldehyde, 3-methyl-1-butene, and 2-methyl-2-butene. Moreover, some concentrate formulations have contained hazardous additives such as pine rosin and ketene precursors such as cannabinoid acetates. As with nicotine vaping, the presence of oxygen plays a critical role in driving the formation of many toxic chemical degradation products during vaping.</p><p><strong>Conclusion: </strong>Since the legalization of recreational cannabis, concentrates have become one of the most rapidly expanding segments of the U.S. cannabis market. However, research into the specific health risks of vaping these products has significantly lagged their widespread use. The studies presented in this review article highlight the potential for exposure to known toxicants during the vaping of cannabis concentrates.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1568207"},"PeriodicalIF":3.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478127","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":"The patterns of dynamic changes in blood toxicant levels, prognosis, and regression in a case of occupational chlorfenapyr exposure.","authors":"Jianjian Liu, Zhaozhao Shan, Chen Wang, Xiangdong Jian, Baotian Kan, Yingli Ren","doi":"10.3389/ftox.2025.1570887","DOIUrl":"10.3389/ftox.2025.1570887","url":null,"abstract":"<p><strong>Objective: </strong>In July 2024, cases of chlorfenapyr poisoning occurred consecutively among workers in a chlorfenapyr production plant in Shandong Province. This study aimed to analyze the clinical characteristics of this event and discuss the significance of toxicant testing and imaging examinations in guiding clinical practice.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical data of four patients with occupational chlorfenapyr poisoning.</p><p><strong>Results: </strong>All four patients worked in the same factory before admission; three worked in the same workshop, while one worked in the product inspection department. Patients three and four had no obvious clinical manifestations, whereas patients one and two primarily presented with hyperhidrosis, fever, and neurological symptoms. Laboratory tests revealed abnormalities in blood counts, liver and kidney function indicators, and cardiac enzyme profiles in some patients. Magnetic resonance imaging revealed varying degrees of abnormal signal changes in the brain and spinal cord in Patients 1, 2, and 3. After comprehensive treatment with blood purification, organ protection, and symptomatic treatment, chlorfenapyr blood concentrations in patients 1, 2, and 3 decreased. Patients one and three were discharged on the 30th and 14th days of admission, respectively, while patient 2, whose condition worsened, died on the 11th day of treatment after unsuccessful resuscitation.</p><p><strong>Conclusion: </strong>Patients with occupational chlorfenapyr poisoning may have no obvious clinical symptoms or may present with excessive sweating and fatigue in the early stages, unlike patients who have ingested chlorfenapyr orally. Therefore, early detection and imaging examinations are crucial for an accurate diagnosis.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1570887"},"PeriodicalIF":3.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478128","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}
Frontiers in toxicologyPub Date : 2025-06-04eCollection Date: 2025-01-01DOI: 10.3389/ftox.2025.1600127
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
{"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":"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}