Pub Date : 2025-11-04DOI: 10.1016/j.toxrep.2025.102162
Ho Young Lee , Choon-Myung Lee , Zachery R. Jarrell , ViLinh Tran , M. Ryan Smith , Dean P. Jones , Young-Mi Go
Cadmium (Cd) is a pervasive environmental metal that bioaccumulates in humans and causes lung disease. Deltamethrin (DM) is a pyrethroid insecticide that is used widely in agriculture, commercial, and residential areas. Both Cd and DM impair mitochondrial function, but responses to combined DM plus Cd have not been studied. The purpose of this study was to test DM and Cd effects on mitochondrial metabolism, bioenergetic activities, and reactive oxidant production in human lung fibroblasts. Metabolomics analyses with liquid chromatography-high resolution mass spectrometry were used to analyze mitochondrial metabolic effects. Extracellular flux analyses were used to measure mitochondrial bioenergetics. Fluorescence cytochemistry was used to measure mitochondrial oxidant production. The results show that mitochondrial metabolic perturbations were greatest with DM plus Cd, with significant effects on the citric acid cycle, along with increased collagen amino acids, proline, and hydroxyproline, indicators of fibrotic activity. Mitochondria bioenergetics, including basal, maximal, and ATP-linked respiration, were inhibited by Cd, with greater effects due to DM and Cd plus DM. Mitochondrial superoxide production was greatest with Cd plus DM. Taken together, this study shows that low environmental levels of DM and Cd cause changes in mitochondrial bioenergetics and metabolism in human lung fibroblasts consistent with adverse effects in lung disease.
{"title":"The effects of combined low-dose cadmium and deltamethrin on mitochondrial bioenergetics and metabolism in human lung fibroblasts","authors":"Ho Young Lee , Choon-Myung Lee , Zachery R. Jarrell , ViLinh Tran , M. Ryan Smith , Dean P. Jones , Young-Mi Go","doi":"10.1016/j.toxrep.2025.102162","DOIUrl":"10.1016/j.toxrep.2025.102162","url":null,"abstract":"<div><div>Cadmium (Cd) is a pervasive environmental metal that bioaccumulates in humans and causes lung disease. Deltamethrin (DM) is a pyrethroid insecticide that is used widely in agriculture, commercial, and residential areas. Both Cd and DM impair mitochondrial function, but responses to combined DM plus Cd have not been studied. The purpose of this study was to test DM and Cd effects on mitochondrial metabolism, bioenergetic activities, and reactive oxidant production in human lung fibroblasts. Metabolomics analyses with liquid chromatography-high resolution mass spectrometry were used to analyze mitochondrial metabolic effects. Extracellular flux analyses were used to measure mitochondrial bioenergetics. Fluorescence cytochemistry was used to measure mitochondrial oxidant production. The results show that mitochondrial metabolic perturbations were greatest with DM plus Cd, with significant effects on the citric acid cycle, along with increased collagen amino acids, proline, and hydroxyproline, indicators of fibrotic activity. Mitochondria bioenergetics, including basal, maximal, and ATP-linked respiration, were inhibited by Cd, with greater effects due to DM and Cd plus DM. Mitochondrial superoxide production was greatest with Cd plus DM. Taken together, this study shows that low environmental levels of DM and Cd cause changes in mitochondrial bioenergetics and metabolism in human lung fibroblasts consistent with adverse effects in lung disease.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102162"},"PeriodicalIF":0.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.toxrep.2025.102157
Michael Ankapong , Gerheart Winfred Ashong , Albert Amatey Adjaottor , Boansi Adu Ababio , Edward Ebow Kwaansa-Ansah , Mandela Toku
Arsenic contamination in groundwater poses global health risks, but safe removal and disposal remain a significant concern for groundwater owners in developing countries. This study aimed to evaluate the health risks, sources, and concentration of arsenic species in groundwater from Sanso, Ghana, and further synthesize and characterize magnetic activated carbon (Fe-CAC) for arsenic removal, and solidify and stabilize the arsenic loaded onto Fe-CAC using cement, nickel oxide, and eggshell waste (AFCNE). Groundwater samples were collected from the Sanso community in Ghana. Arsenic speciation was determined using standard analytical methods and a flame atomic absorption spectrophotometer. Scanning electron microscopy, X-ray diffraction analysis, and Fourier transform infrared spectroscopy analysis were used to characterize the materials. The findings revealed that mean concentrations of total arsenic (15.463 μg/L) and arsenite (13.645 μg/L) did not conform to the WHO guideline value of 10 μg/L. The multivariate analysis revealed impacts of illegal mining activities, geological influences, and geochemical conditions strongly influencing arsenic enrichment and transport in aquifers. Children showed a higher chronic daily exposure to arsenic than adults, with oral exposure being significantly higher than dermal exposure. The cumulative carcinogenic and non-carcinogenic risk exceeded 10−4 and 1, respectively, indicating a high potential for skin cancer, bronchitis, and skin lesions. The Fe-CAC adsorption minimized arsenic concentrations from 15.463 to 0.0302 μg/L, accomplishing a removal efficiency of 99.769 %, proving its effectiveness in treating arsenic in groundwater. The leaching test showed a significant reduction in arsenic release, ranging from 1.32 to 0.20 μg/L below the USEPA limit of 5 μg/L, indicating AFCNE long-term stability in immobilizing arsenic and its suitability for safe landfill disposal. This study suggests the need for integrated remediation strategies for long-term arsenic mitigation, continuous monitoring, community awareness, and swift implementation of effective water policy interventions for sustainable groundwater quality.
{"title":"Assessment and management of arsenic contamination in groundwater from Sanso, Ghana: Health risk implications, source identification, adsorption and immobilization for safe disposal","authors":"Michael Ankapong , Gerheart Winfred Ashong , Albert Amatey Adjaottor , Boansi Adu Ababio , Edward Ebow Kwaansa-Ansah , Mandela Toku","doi":"10.1016/j.toxrep.2025.102157","DOIUrl":"10.1016/j.toxrep.2025.102157","url":null,"abstract":"<div><div>Arsenic contamination in groundwater poses global health risks, but safe removal and disposal remain a significant concern for groundwater owners in developing countries. This study aimed to evaluate the health risks, sources, and concentration of arsenic species in groundwater from Sanso, Ghana, and further synthesize and characterize magnetic activated carbon (Fe-CAC) for arsenic removal, and solidify and stabilize the arsenic loaded onto Fe-CAC using cement, nickel oxide, and eggshell waste (AFCNE). Groundwater samples were collected from the Sanso community in Ghana. Arsenic speciation was determined using standard analytical methods and a flame atomic absorption spectrophotometer. Scanning electron microscopy, X-ray diffraction analysis, and Fourier transform infrared spectroscopy analysis were used to characterize the materials. The findings revealed that mean concentrations of total arsenic (15.463 μg/L) and arsenite (13.645 μg/L) did not conform to the WHO guideline value of 10 μg/L. The multivariate analysis revealed impacts of illegal mining activities, geological influences, and geochemical conditions strongly influencing arsenic enrichment and transport in aquifers. Children showed a higher chronic daily exposure to arsenic than adults, with oral exposure being significantly higher than dermal exposure. The cumulative carcinogenic and non-carcinogenic risk exceeded 10<sup>−4</sup> and 1, respectively, indicating a high potential for skin cancer, bronchitis, and skin lesions. The Fe-CAC adsorption minimized arsenic concentrations from 15.463 to 0.0302 μg/L, accomplishing a removal efficiency of 99.769 %, proving its effectiveness in treating arsenic in groundwater. The leaching test showed a significant reduction in arsenic release, ranging from 1.32 to 0.20 μg/L below the USEPA limit of 5 μg/L, indicating AFCNE long-term stability in immobilizing arsenic and its suitability for safe landfill disposal. This study suggests the need for integrated remediation strategies for long-term arsenic mitigation, continuous monitoring, community awareness, and swift implementation of effective water policy interventions for sustainable groundwater quality.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102157"},"PeriodicalIF":0.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-03DOI: 10.1016/j.toxrep.2025.102160
Asmaa Fady Sharif , Badar Abdullah Al Qasem , Muhannad Abdullah Alsaidan , Abdulaziz Adel Al Abdulkader , Sultan Abdulhamid Albisher , Mesfer Mubarak Hanif , Bandar Saleh Aldurayb , Mohammad Abdullah AL-Otaibi , Abeer Jaber Mohamed , Fahad aldosari , Khalid A. Al-Mulhim , Zahraa Khalifa Sobh
Toxic alcohols are readily available in multiple household products. Although acute toxic alcohol exposure is less frequently reported, it results in severe consequences. This study aimed to evaluate the effectiveness of the three elements score, PGI]pH, Glasgow Coma Scale (GCS), and Impaired systolic blood pressure (SBP)] score and its two elements modified PG (pH and GCS) score, in identifying high-risk alcohol-exposed patients, compared to the multivariable conventional poison severity score (PSS). This cross-sectional study was conducted among 80 patients admitted to two poison control centers over a five-year period. These patients were exposed to toxic alcohols, including methanol, glycols, and propanol. The PGI/PG scores were derived retrospectively by assigning one point for every adopted variable, including pH < 7.25, GCS < 13, and impaired SBP < 90 mmHg. Patients with unfavorable outcomes constituted 27.5 %, where 17.5 % underwent hemodialysis (HD), 6.3 % developed blindness, 5 % needed mechanical ventilation (MV), and 2.5 % died. Patients with unfavorable outcomes demonstrated significantly higher PSS, PGI, and PG scores (p < 0.05). PSS was superior in predicting blindness only. PGI and PG scores demonstrated higher capabilities for predicting unfavorable outcomes, as well as the need for HD and MV. PG achieved the highest areas under curve as an unfavorable outcome’s predictor (0.889), need for HD (0.819), and MV (0.993). The PGI and PG scores could serve as simple and reliable predictors of unfavorable outcomes, including the need for HD and MV among patients poisoned with acute toxic alcohol exposure.
{"title":"Less is more: Evaluating the effectiveness of simplified two and three-element scores for predicting unfavorable outcomes in acute toxic alcohol exposure: A multi-center study","authors":"Asmaa Fady Sharif , Badar Abdullah Al Qasem , Muhannad Abdullah Alsaidan , Abdulaziz Adel Al Abdulkader , Sultan Abdulhamid Albisher , Mesfer Mubarak Hanif , Bandar Saleh Aldurayb , Mohammad Abdullah AL-Otaibi , Abeer Jaber Mohamed , Fahad aldosari , Khalid A. Al-Mulhim , Zahraa Khalifa Sobh","doi":"10.1016/j.toxrep.2025.102160","DOIUrl":"10.1016/j.toxrep.2025.102160","url":null,"abstract":"<div><div>Toxic alcohols are readily available in multiple household products. Although acute toxic alcohol exposure is less frequently reported, it results in severe consequences. This study aimed to evaluate the effectiveness of the three elements score, PGI]pH, Glasgow Coma Scale (GCS), and Impaired systolic blood pressure (SBP)] score and its two elements modified PG (pH and GCS) score, in identifying high-risk alcohol-exposed patients, compared to the multivariable conventional poison severity score (PSS). This cross-sectional study was conducted among 80 patients admitted to two poison control centers over a five-year period. These patients were exposed to toxic alcohols, including methanol, glycols, and propanol. The PGI/PG scores were derived retrospectively by assigning one point for every adopted variable, including pH < 7.25, GCS < 13, and impaired SBP < 90 mmHg. Patients with unfavorable outcomes constituted 27.5 %, where 17.5 % underwent hemodialysis (HD), 6.3 % developed blindness, 5 % needed mechanical ventilation (MV), and 2.5 % died. Patients with unfavorable outcomes demonstrated significantly higher PSS, PGI, and PG scores (p < 0.05). PSS was superior in predicting blindness only. PGI and PG scores demonstrated higher capabilities for predicting unfavorable outcomes, as well as the need for HD and MV. PG achieved the highest areas under curve as an unfavorable outcome’s predictor (0.889), need for HD (0.819), and MV (0.993). The PGI and PG scores could serve as simple and reliable predictors of unfavorable outcomes, including the need for HD and MV among patients poisoned with acute toxic alcohol exposure.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102160"},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chios mastic gum (CMG) exhibits several pharmacological activities that have been confirmed by numerous studies. These include antibacterial, anti-inflammatory, hypolipidemic, hypoglycemic, antiatheromatic, and benefits for against gastrointestinal disorders. However, studies focusing on CMG’s safety are limited. The aim of the present study is to evaluate the genotoxicity of CMG using the limit test on the mammalian erythrocyte micronucleus assay, in male Wistar rats. CMG was administered by gavage to 5 rats at 2000 mg/kg bw for 3 days, while 5 rats received the vehicle and 5 rats received cyclophosphamide (positive control). Satellite groups of 3 rats were included for the negative control and CMG-treated groups to collect plasma and bone marrow for the chemical analyses. All rats were observed for mortality and clinical signs of toxicity during the dosing period. Rats were euthanatized 20 h after the last treatment, necropsied, and bone marrow was collected for smear preparation. No mortality, clinical signs of toxicity, gross organ pathology, or body weight changes were observed in CMG-treated rats compared to the negative control group. No statistically significant alteration of polychromatic erythrocytes (PCE) and the per-thousand incidences of micronucleated PCE in the bone marrow of CMG-treated rats were observed. Bone marrow exposure to CMG was unambiguously confirmed by the detection of the characteristic CMG triterpenic acids in both bone marrow extract and plasma of CMG-treated rats by UHPLC-HRMS/MS analysis. In conclusion, CMG exhibited no genotoxic effects on bone marrow erythrocytes at the tested limit dose of 2000mg/kg body weight.
{"title":"In vivo genotoxicity of Chios mastic gum in rodent bone marrow micronucleus test","authors":"Eirini-Christina Psarou , Aikaterini Termentzi , Katerina Kyriakopoulou , Pelagia Anastasiadou , Marios Meidanis , Nikolas Fokialakis , Kyriaki Machera","doi":"10.1016/j.toxrep.2025.102155","DOIUrl":"10.1016/j.toxrep.2025.102155","url":null,"abstract":"<div><div>Chios mastic gum (CMG) exhibits several pharmacological activities that have been confirmed by numerous studies. These include antibacterial, anti-inflammatory, hypolipidemic, hypoglycemic, antiatheromatic, and benefits for against gastrointestinal disorders. However, studies focusing on CMG’s safety are limited. The aim of the present study is to evaluate the genotoxicity of CMG using the limit test on the mammalian erythrocyte micronucleus assay, in male Wistar rats. CMG was administered by gavage to 5 rats at 2000 mg/kg bw for 3 days, while 5 rats received the vehicle and 5 rats received cyclophosphamide (positive control). Satellite groups of 3 rats were included for the negative control and CMG-treated groups to collect plasma and bone marrow for the chemical analyses. All rats were observed for mortality and clinical signs of toxicity during the dosing period. Rats were euthanatized 20 h after the last treatment, necropsied, and bone marrow was collected for smear preparation. No mortality, clinical signs of toxicity, gross organ pathology, or body weight changes were observed in CMG-treated rats compared to the negative control group. No statistically significant alteration of polychromatic erythrocytes (PCE) and the per-thousand incidences of micronucleated PCE in the bone marrow of CMG-treated rats were observed. Bone marrow exposure to CMG was unambiguously confirmed by the detection of the characteristic CMG triterpenic acids in both bone marrow extract and plasma of CMG-treated rats by UHPLC-HRMS/MS analysis. In conclusion, CMG exhibited no genotoxic effects on bone marrow erythrocytes at the tested limit dose of 2000mg/kg body weight.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102155"},"PeriodicalIF":0.0,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.toxrep.2025.102154
Alise D.E. de Groot , Willemien F.J. Hof , Hester van Meer , Niels de Vries , Daan J. Touw , Alwin D.R. Huitema , Paola Mian
Tamoxifen is a selective oestrogen receptor modulator indicated for the treatment of breast cancer in adults. The recommended dose is 20 mg orally once daily. We report an accidental tamoxifen ingestion in a 2-year-old female who accessed the tamoxifen from a pill bottle stored in a bag while unsupervised. Activated charcoal and sodium sulphate were administered approximately 2.5 h after ingestion. Plasma concentrations of both tamoxifen and active metabolite endoxifen were determined. The maximum plasma concentration of tamoxifen was 53.8 ng/mL, occurring two hours after ingestion. In contrast, the plasma concentration of endoxifen measured at 22 h after ingestion was 0.771 ng/L, which is considered subtherapeutic in adults. However, given the prolonged half-life of endoxifen, the plasma levels may still be rising at this point. The ingested dose was estimated to be around 31–37 mg, based on the plasma levels of tamoxifen and endoxifen. The actual ingested amount may have been higher due to early oral administration of activated charcoal. No direct serious events occurred during a hospital admission of 31 h. Given the anti-oestrogen properties of tamoxifen and the critical role of oestrogen in pubertal development long-term follow-up is recommended to monitor potential delayed effects.
{"title":"Accidental tamoxifen ingestion in a two-year-old child without major immediate symptoms: Case report","authors":"Alise D.E. de Groot , Willemien F.J. Hof , Hester van Meer , Niels de Vries , Daan J. Touw , Alwin D.R. Huitema , Paola Mian","doi":"10.1016/j.toxrep.2025.102154","DOIUrl":"10.1016/j.toxrep.2025.102154","url":null,"abstract":"<div><div>Tamoxifen is a selective oestrogen receptor modulator indicated for the treatment of breast cancer in adults. The recommended dose is 20 mg orally once daily. We report an accidental tamoxifen ingestion in a 2-year-old female who accessed the tamoxifen from a pill bottle stored in a bag while unsupervised. Activated charcoal and sodium sulphate were administered approximately 2.5 h after ingestion. Plasma concentrations of both tamoxifen and active metabolite endoxifen were determined. The maximum plasma concentration of tamoxifen was 53.8 ng/mL, occurring two hours after ingestion. In contrast, the plasma concentration of endoxifen measured at 22 h after ingestion was 0.771 ng/L, which is considered subtherapeutic in adults. However, given the prolonged half-life of endoxifen, the plasma levels may still be rising at this point. The ingested dose was estimated to be around 31–37 mg, based on the plasma levels of tamoxifen and endoxifen. The actual ingested amount may have been higher due to early oral administration of activated charcoal. No direct serious events occurred during a hospital admission of 31 h. Given the anti-oestrogen properties of tamoxifen and the critical role of oestrogen in pubertal development long-term follow-up is recommended to monitor potential delayed effects.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102154"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.toxrep.2025.102153
Sarbani Hazra , Aditya Konar , Robb Welty , Uday B. Kompella
Arsenical ocular toxicity is acute, painful, and aggressive. Although British anti-Lewisite (BAL) is an approved therapy for systemic arsenical toxicity, remedial measure for ocular exposure of arsenicals is still an unmet need. This study evaluated the efficacy of BAL as topical drop for ameliorating the pathogenesis incited by phenylarsine oxide (PAO, surrogate for lewisite), a chemical warfare agent. The binding of BAL to arsenic and calcium and zinc, two essential cellular minerals was determined using Isothermal Titration Calorimetry (ITC). Ex vivo, mouse corneas were tested with various concentrations of BAL (0.1 %, 1 %, and 5 %). Injury was induced ex vivo using PAO, 25 µg/5 µL, and rescue was evaluated with 1 % BAL. In-vivo, injury to mouse cornea was induced with PAO 100 µg/5 µL and rescue was evaluated by 1 % BAL. All eyes were assessed for physical symptoms by examination under slit lamp biomicroscope, anterior segment optical coherence tomography (AS-OCT), corneal thickness, and histopathological changes. BAL bonded strongly with arsenic but negligibly with calcium and zinc. Ex-vivo cornea, response with 1 % BAL was graded superior to higher concentration. One of eight mice with PAO injury survived versus all survivals in the PAO+BAL group after injury. Topical use of BAL mitigated the exacerbated ocular response exhibited by PAO injury. Histology revealed better preservation of retinal architecture in BAL treated mice. 1 % BAL alleviates PAO induced fatality in mice. The rescue in the posterior segment pathogenesis was remarkable. BAL is a promising decontaminant for ocular arsenical exposure and warrants further investigation.
{"title":"British anti-Lewisite (BAL) reduces the severity of systemic and local responses of the eye after exposure to the chemical warfare agent surrogate for Lewisite, phenylarsine oxide (PAO)","authors":"Sarbani Hazra , Aditya Konar , Robb Welty , Uday B. Kompella","doi":"10.1016/j.toxrep.2025.102153","DOIUrl":"10.1016/j.toxrep.2025.102153","url":null,"abstract":"<div><div>Arsenical ocular toxicity is acute, painful, and aggressive. Although British anti-Lewisite (BAL) is an approved therapy for systemic arsenical toxicity, remedial measure for ocular exposure of arsenicals is still an unmet need. This study evaluated the efficacy of BAL as topical drop for ameliorating the pathogenesis incited by phenylarsine oxide (PAO, surrogate for lewisite), a chemical warfare agent. The binding of BAL to arsenic and calcium and zinc, two essential cellular minerals was determined using Isothermal Titration Calorimetry (ITC). Ex vivo, mouse corneas were tested with various concentrations of BAL (0.1 %, 1 %, and 5 %). Injury was induced ex vivo using PAO, 25 µg/5 µL, and rescue was evaluated with 1 % BAL. In-vivo, injury to mouse cornea was induced with PAO 100 µg/5 µL and rescue was evaluated by 1 % BAL. All eyes were assessed for physical symptoms by examination under slit lamp biomicroscope, anterior segment optical coherence tomography (AS-OCT), corneal thickness, and histopathological changes. BAL bonded strongly with arsenic but negligibly with calcium and zinc. Ex-vivo cornea, response with 1 % BAL was graded superior to higher concentration. One of eight mice with PAO injury survived versus all survivals in the PAO+BAL group after injury. Topical use of BAL mitigated the exacerbated ocular response exhibited by PAO injury. Histology revealed better preservation of retinal architecture in BAL treated mice. 1 % BAL alleviates PAO induced fatality in mice. The rescue in the posterior segment pathogenesis was remarkable. BAL is a promising decontaminant for ocular arsenical exposure and warrants further investigation.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102153"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.toxrep.2025.102152
Kaustuv Basu , James Li, Luc Mongeau
Electronic (e)-cigarette and e-liquid exposure have been linked to vocal fold inflammation and dysphonia, yet no targeted non-surgical therapies currently exist. Hyaluronan, a key extracellular matrix component essential for vocal fold structure, repair, and function, is known to be dysregulated in inflammatory conditions; however, its metabolic gene response to e-liquid exposure in human vocal fold fibroblasts (hVFFs) remains uncharacterized. Hence, it is critical to understand hyaluronan metabolic gene expression under e-liquid toxicity to develop novel drug discovery strategies for vocal fold inflammation. To avoid confounding effects from thermal degradation and aerosol variability in conventional vapor models, hVFFs were exposed to nicotine-containing unvaporized e-liquid (0.125–1 mg/mL) for 24 h, revealing concentration-dependent changes in cell morphology and viability (p < 0.05). The lethal concentration 50 (LC₅₀) was determined to be 0.437 mg/mL and used for short-term (24 h) and extended (72–96 h) exposures. Extended exposure induced intracellular reactive oxygen species (ROS), inflammation, suppressed collagenolysis, and increased the collagen 1 A: collagen 3 A ratio, suggesting fibrotic remodeling. Short-term exposure downregulated hyaluronan synthases (HAS1, HAS2, HAS3) and catabolic genes (HYAL2, CD44), reducing extracellular hyaluronan levels. In contrast, extended exposure repressed HAS1 and HAS2 while upregulating HAS3, CD44, and HYAL2, indicating enhanced hyaluronan degradation and accumulation of proinflammatory low molecular weight hyaluronan. CD44 silencing reduced IL-8 mRNA expression, confirming its role in hVFF inflammation. These findings provide the first mechanistic insight into unvaporized e-liquid-induced dysregulation of hyaluronan metabolism in hVFFs, offering a foundation for biomarker identification and therapeutic development targeting e-cigarette-associated vocal fold inflammation.
{"title":"Unvaporized e-liquid toxicity elevates CD44-dependent hyaluronan catabolic gene expression and triggers inflammation in human vocal fold fibroblasts","authors":"Kaustuv Basu , James Li, Luc Mongeau","doi":"10.1016/j.toxrep.2025.102152","DOIUrl":"10.1016/j.toxrep.2025.102152","url":null,"abstract":"<div><div>Electronic (e)-cigarette and e-liquid exposure have been linked to vocal fold inflammation and dysphonia, yet no targeted non-surgical therapies currently exist. Hyaluronan, a key extracellular matrix component essential for vocal fold structure, repair, and function, is known to be dysregulated in inflammatory conditions; however, its metabolic gene response to e-liquid exposure in human vocal fold fibroblasts (hVFFs) remains uncharacterized. Hence, it is critical to understand hyaluronan metabolic gene expression under e-liquid toxicity to develop novel drug discovery strategies for vocal fold inflammation. To avoid confounding effects from thermal degradation and aerosol variability in conventional vapor models, hVFFs were exposed to nicotine-containing unvaporized e-liquid (0.125–1 mg/mL) for 24 h, revealing concentration-dependent changes in cell morphology and viability (p < 0.05). The lethal concentration 50 (LC₅₀) was determined to be 0.437 mg/mL and used for short-term (24 h) and extended (72–96 h) exposures. Extended exposure induced intracellular reactive oxygen species (ROS), inflammation, suppressed collagenolysis, and increased the collagen 1 A: collagen 3 A ratio, suggesting fibrotic remodeling. Short-term exposure downregulated hyaluronan synthases (HAS1, HAS2, HAS3) and catabolic genes (HYAL2, CD44), reducing extracellular hyaluronan levels. In contrast, extended exposure repressed HAS1 and HAS2 while upregulating HAS3, CD44, and HYAL2, indicating enhanced hyaluronan degradation and accumulation of proinflammatory low molecular weight hyaluronan. CD44 silencing reduced <em>IL-8</em> mRNA expression, confirming its role in hVFF inflammation. These findings provide the first mechanistic insight into unvaporized e-liquid-induced dysregulation of hyaluronan metabolism in hVFFs, offering a foundation for biomarker identification and therapeutic development targeting e-cigarette-associated vocal fold inflammation.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102152"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.toxrep.2025.102150
Albin Stjernbrandt
Diisocyanates are a group of chemicals used in many different applications, such as plastics, foams, coatings, adhesives, and sealants. Prolonged occupational exposure can result in severe asthma. This case report presents a non-smoking male without any previous respiratory disease, where severe obstructive airway symptoms developed during a single event with high airborne exposure to polyurethane foam containing methylene diphenyl diisocyanate during the coating of a large vehicle. The subject was subsequently diagnosed with occupational asthma based on a significant variability in a two-week peak expiratory flow curve and a positive metacholine challenge. Despite aborted exposure and optimized asthma treatment, the subject continued to experience debilitating airway symptoms. This case report demonstrates that severe asthma can develop following a single exposure to polyurethane foam containing methylene diphenyl diisocyanate, underscoring the importance of preventive measures in workplaces where such chemicals are used.
{"title":"Occupational asthma following single exposure to polyurethane foam containing methylene diphenyl diisocyanate – A case report","authors":"Albin Stjernbrandt","doi":"10.1016/j.toxrep.2025.102150","DOIUrl":"10.1016/j.toxrep.2025.102150","url":null,"abstract":"<div><div>Diisocyanates are a group of chemicals used in many different applications, such as plastics, foams, coatings, adhesives, and sealants. Prolonged occupational exposure can result in severe asthma. This case report presents a non-smoking male without any previous respiratory disease, where severe obstructive airway symptoms developed during a single event with high airborne exposure to polyurethane foam containing methylene diphenyl diisocyanate during the coating of a large vehicle. The subject was subsequently diagnosed with occupational asthma based on a significant variability in a two-week peak expiratory flow curve and a positive metacholine challenge. Despite aborted exposure and optimized asthma treatment, the subject continued to experience debilitating airway symptoms. This case report demonstrates that severe asthma can develop following a single exposure to polyurethane foam containing methylene diphenyl diisocyanate, underscoring the importance of preventive measures in workplaces where such chemicals are used.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102150"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.toxrep.2025.102149
Henrique Spaulonci Silveira , Roberta Carvalho Cesário , Vinicius Augusto Simão , Fernando Guimarães , Fábio Rodrigues Ferreira Seiva , Debora Aparecida P.C. Zuccari , Glaura Scantamburlo Alves Fernandes , Milena Cremer de Souza , Russel J. Reiter , Luiz Gustavo de Almeida Chuffa
Ovarian cancer (OC), a highly recurrent and fatal tumor, poses diagnostic challenges due to generic symptoms and chemoresistance. Melatonin (Mel) is an indoleamine acting against tumor progression and exhibiting pro-oxidative actions in tumor cells. This in vitro study explores the impact of Mel on antioxidant defenses of OC cells (high-grade SKOV-3 and low-grade CAISMOV-24 lines), focusing on its receptor-dependent and -independent effects. Cell viability was evaluated through MTT assay and antioxidant system was assessed in supernatants by measuring glutathione (GS), reduced (GSH) and oxidized (GSSG) glutathione, catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD). Mel accumulated intracellularly and exerted cytotoxic effects, reducing cell viability in both cell lines. Notably, Mel independently of its membrane receptors, inhibited migration and invasion, thus showing its anti-tumoral potential. By investigating melatonin’s actions, we observed an impact on the antioxidant system primarily through the reduced activity of CAT and the GS axis. The modulation of these antioxidants by Mel demonstrates its multifaceted role in OC, emphasizing its therapeutic potential. We also demonstrated, for the first time, the theoretical ability of Mel to bind to CAT, which may be responsible for the reduction in enzyme activity. This study provides novel insights into Mel's receptor-independent actions and supports its potential as an adjuvant therapeutic agent in OC.
{"title":"Melatonin promotes cytotoxicity while reducing cell motility and antioxidant defenses in ovarian cancer cell lines","authors":"Henrique Spaulonci Silveira , Roberta Carvalho Cesário , Vinicius Augusto Simão , Fernando Guimarães , Fábio Rodrigues Ferreira Seiva , Debora Aparecida P.C. Zuccari , Glaura Scantamburlo Alves Fernandes , Milena Cremer de Souza , Russel J. Reiter , Luiz Gustavo de Almeida Chuffa","doi":"10.1016/j.toxrep.2025.102149","DOIUrl":"10.1016/j.toxrep.2025.102149","url":null,"abstract":"<div><div>Ovarian cancer (OC), a highly recurrent and fatal tumor, poses diagnostic challenges due to generic symptoms and chemoresistance. Melatonin (Mel) is an indoleamine acting against tumor progression and exhibiting pro-oxidative actions in tumor cells. This in vitro study explores the impact of Mel on antioxidant defenses of OC cells (high-grade SKOV-3 and low-grade CAISMOV-24 lines), focusing on its receptor-dependent and -independent effects. Cell viability was evaluated through MTT assay and antioxidant system was assessed in supernatants by measuring glutathione (GS), reduced (GSH) and oxidized (GSSG) glutathione, catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD). Mel accumulated intracellularly and exerted cytotoxic effects, reducing cell viability in both cell lines. Notably, Mel independently of its membrane receptors, inhibited migration and invasion, thus showing its anti-tumoral potential. By investigating melatonin’s actions, we observed an impact on the antioxidant system primarily through the reduced activity of CAT and the GS axis. The modulation of these antioxidants by Mel demonstrates its multifaceted role in OC, emphasizing its therapeutic potential. We also demonstrated, for the first time, the theoretical ability of Mel to bind to CAT, which may be responsible for the reduction in enzyme activity. This study provides novel insights into Mel's receptor-independent actions and supports its potential as an adjuvant therapeutic agent in OC.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102149"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.toxrep.2025.102151
Christina Hoyer-Kimura , John P. Konhilas , Meredith Hay
PNA5 is a novel pleotropic anti-inflammatory glycosylated-Angiotensin-(1−7) peptide derivative with outstanding brain penetration and enhanced bioavailability. PNA5, via the Mas receptor, decreases brain and cerebrovascular inflammation, reduces reactive oxygen species and inflammatory cytokines production, improves cerebral blood flow, and restores cognitive function in our mouse model of VCID (Vascular contributions to cognitive impairment and dementia). This study evaluated the potential systemic and local toxicity and toxicokinetic (TK) of PNA5 following daily subcutaneous administration in Sprague Dawley rats and Beagle dogs for 28 consecutive days. PNA5 was given at 1, 5, 40 mg/kg/day to rats (n = 12) and at 1, 5, and 20 mg/kg/day in dogs (n = 6) once daily for 28 consecutive days. Blood samples were collected on days 1 and 28 for TK analysis. PNA5 was well tolerated at all doses in both species, with no test article-related mortality or adverse effects. Systemic exposure to PNA5 appeared to be independent of sex. In rats, Cmax and AUC0–2hr values increased with increasing doses. Systemic exposure to PNA5 in rats was greater on day 28 compared to day 1 following repeated administration of PNA5. In dogs, Cmax values increased less than dose-proportionally, and AUC0–2hr increased approximately dose-proportionally on days 1 and 28. Systemic exposure to PNA5 in dogs was similar on days 1 and 28 following repeated administration. These results show that PNA5 has no toxicological effects at the highest doses tested in rats or dogs and is well tolerated with repeated exposure for 28 days. Accumulation was observed in rats but not in dogs.
{"title":"PNA5, a glycosylated angiotensin-(1−7) mas receptor agonist for vascular dementia: A two species toxicology and toxicokinetic study","authors":"Christina Hoyer-Kimura , John P. Konhilas , Meredith Hay","doi":"10.1016/j.toxrep.2025.102151","DOIUrl":"10.1016/j.toxrep.2025.102151","url":null,"abstract":"<div><div>PNA5 is a novel pleotropic anti-inflammatory glycosylated-Angiotensin-(1−7) peptide derivative with outstanding brain penetration and enhanced bioavailability. PNA5, via the Mas receptor, decreases brain and cerebrovascular inflammation, reduces reactive oxygen species and inflammatory cytokines production, improves cerebral blood flow, and restores cognitive function in our mouse model of VCID (Vascular contributions to cognitive impairment and dementia). This study evaluated the potential systemic and local toxicity and toxicokinetic (TK) of PNA5 following daily subcutaneous administration in Sprague Dawley rats and Beagle dogs for 28 consecutive days. PNA5 was given at 1, 5, 40 mg/kg/day to rats (n = 12) and at 1, 5, and 20 mg/kg/day in dogs (n = 6) once daily for 28 consecutive days. Blood samples were collected on days 1 and 28 for TK analysis. PNA5 was well tolerated at all doses in both species, with no test article-related mortality or adverse effects. Systemic exposure to PNA5 appeared to be independent of sex. In rats, Cmax and AUC<sub>0–2hr</sub> values increased with increasing doses. Systemic exposure to PNA5 in rats was greater on day 28 compared to day 1 following repeated administration of PNA5. In dogs, Cmax values increased less than dose-proportionally, and AUC<sub>0–2hr</sub> increased approximately dose-proportionally on days 1 and 28. Systemic exposure to PNA5 in dogs was similar on days 1 and 28 following repeated administration. These results show that PNA5 has no toxicological effects at the highest doses tested in rats or dogs and is well tolerated with repeated exposure for 28 days. Accumulation was observed in rats but not in dogs.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102151"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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