Pub Date : 2025-09-11eCollection Date: 2025-12-01DOI: 10.1016/j.toxrep.2025.102126
Hector A Cabrera-Fuentes, Klaus T Preissner
{"title":"Extracellular RNA in iron-induced hepatic injury: Beyond TLR3 toward an integrated inflammatory axis.","authors":"Hector A Cabrera-Fuentes, Klaus T Preissner","doi":"10.1016/j.toxrep.2025.102126","DOIUrl":"10.1016/j.toxrep.2025.102126","url":null,"abstract":"","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"102126"},"PeriodicalIF":0.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865579","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}
Pub Date : 2025-09-10DOI: 10.1016/j.toxrep.2025.102127
Berber C. Hospes , Elise M.A. Slob , Tom K. Brinkman , Sharif M. Pasha , Erik B. Wilms , Hans W.P.M. Overdiek
Survival after high-dose oral cyanide ingestion is rare, and when untreated cases often result in death within an hour. Immediate treatment however, can be lifesaving. We describe a patient who fully recovered after prompt intervention. He arrived at the emergency department unconscious, with red skin and a Glasgow Coma Scale of 3 and was suspected of an intentional intoxication with an unknown white crystalline powder. He rapidly suffered a cardiac arrest. Blood gas analysis showed severe metabolic acidosis, high lactate, and slightly elevated methemoglobin. In suspect of cyanide poisoning, hydroxocobalamin (2 doses of 5 g intravenous) and sodium thiosulfate (12.5 g intravenous) were administered. Thereafter spontaneous circulation returned. The patient was intubated and sedated in the intensive care unit for four days. After extubation, he was transferred to a general ward. A magnetic resonance imaging scan showed no post-anoxic or toxic damage. During his 14-day stay, he fully recovered. The white powder was identified in the pharmaceutical laboratory by infrared spectrometry, confirming the presence of cyanide. Subsequently, the patient admitted to ingesting potassium cyanide. He obtained the potassium cyanide from his workplace, a chemical laboratory.
{"title":"Surviving cyanide poisoning: A case report highlighting the role of early antidote use","authors":"Berber C. Hospes , Elise M.A. Slob , Tom K. Brinkman , Sharif M. Pasha , Erik B. Wilms , Hans W.P.M. Overdiek","doi":"10.1016/j.toxrep.2025.102127","DOIUrl":"10.1016/j.toxrep.2025.102127","url":null,"abstract":"<div><div>Survival after high-dose oral cyanide ingestion is rare, and when untreated cases often result in death within an hour. Immediate treatment however, can be lifesaving. We describe a patient who fully recovered after prompt intervention. He arrived at the emergency department unconscious, with red skin and a Glasgow Coma Scale of 3 and was suspected of an intentional intoxication with an unknown white crystalline powder. He rapidly suffered a cardiac arrest. Blood gas analysis showed severe metabolic acidosis, high lactate, and slightly elevated methemoglobin. In suspect of cyanide poisoning, hydroxocobalamin (2 doses of 5 g intravenous) and sodium thiosulfate (12.5 g intravenous) were administered. Thereafter spontaneous circulation returned. The patient was intubated and sedated in the intensive care unit for four days. After extubation, he was transferred to a general ward. A magnetic resonance imaging scan showed no post-anoxic or toxic damage. During his 14-day stay, he fully recovered. The white powder was identified in the pharmaceutical laboratory by infrared spectrometry, confirming the presence of cyanide. Subsequently, the patient admitted to ingesting potassium cyanide. He obtained the potassium cyanide from his workplace, a chemical laboratory.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102127"},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044257","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 : 2025-09-09DOI: 10.1016/j.toxrep.2025.102125
Dnyaneshwar Jondhale , Corrine Harris , Gregory S. Ladics
Pig and poultry feed are often included with beta-glucanase to alleviate the anti-nutritional impacts of beta-glucans found in many cereal grains. Safety studies were conducted on beta-glucanase, including skin and eye irritation, dermal sensitization, a 90-day rat oral subchronic study, and genotoxicity, to evaluate the safety of a beta-glucanase for use as an animal feed additive. Beta-glucanase is produced by fermentation with a fungal (Trichoderma reesei) production strain expressing a wild-type fungal endoglucanase (egl2) gene to overexpress the endoglucanase (referred to as beta-glucanase throughout the paper) enzyme. Beta-glucanase was predicted to be non-irritant (No Category) to the skin or eyes in reconstructed human epidermis tissues (RhE) and reconstructed human cornea-like epithelium (RhCE), respectively. Beta-glucanase was tested in vitro in the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). Using the 2 out of 3 approach, beta-glucanase was not a dermal sensitizer based on the negative KeratinoSens™ and h-CLAT assays. In vitro genotoxicity testing confirmed beta-glucanase to be non-genotoxic. In the 90-day subchronic study, rats were administered beta-glucanase daily via oral gavage at dose-levels of 0 (Milli-Q® water), 250, 500 or 1000 mg total organic solids (TOS)/kg bodyweight (bw)/day (equivalent to 0; 42,102; 84,205 and 168,410 units (U)/kg bw/day, respectively). No test item-related adverse effects were observed. A no-observed-adverse-effect level (NOAEL) for beta-glucanase was established at 1000 mg TOS/kg body weight/day, the highest test concentration. Based on this NOAEL and an estimate of consumption determined from the proposed inclusion of the beta-glucanase in feed at the maximum recommended level (426 U/kg), a margin of safety value of 5681 was calculated based on highest expected daily feed intake in broilers, the target species with highest feed intake relative to body weight. The findings support the safe use of beta-glucanase as an animal feed additive.
{"title":"Safety evaluation of a fungal beta-glucanase","authors":"Dnyaneshwar Jondhale , Corrine Harris , Gregory S. Ladics","doi":"10.1016/j.toxrep.2025.102125","DOIUrl":"10.1016/j.toxrep.2025.102125","url":null,"abstract":"<div><div>Pig and poultry feed are often included with beta-glucanase to alleviate the anti-nutritional impacts of beta-glucans found in many cereal grains. Safety studies were conducted on beta-glucanase, including skin and eye irritation, dermal sensitization, a 90-day rat oral subchronic study, and genotoxicity, to evaluate the safety of a beta-glucanase for use as an animal feed additive. Beta-glucanase is produced by fermentation with a fungal (<em>Trichoderma reesei</em>) production strain expressing a wild-type fungal endoglucanase (<em>egl2</em>) gene to overexpress the endoglucanase (referred to as beta-glucanase throughout the paper) enzyme. Beta-glucanase was predicted to be non-irritant (No Category) to the skin or eyes in reconstructed human epidermis tissues (RhE) and reconstructed human cornea-like epithelium (RhCE), respectively. Beta-glucanase was tested <em>in vitro</em> in the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). Using the 2 out of 3 approach, beta-glucanase was not a dermal sensitizer based on the negative KeratinoSens™ and h-CLAT assays. <em>In vitro</em> genotoxicity testing confirmed beta-glucanase to be non-genotoxic. In the 90-day subchronic study, rats were administered beta-glucanase daily via oral gavage at dose-levels of 0 (Milli-Q® water), 250, 500 or 1000 mg total organic solids (TOS)/kg bodyweight (bw)/day (equivalent to 0; 42,102; 84,205 and 168,410 units (U)/kg bw/day, respectively). No test item-related adverse effects were observed. A no-observed-adverse-effect level (NOAEL) for beta-glucanase was established at 1000 mg TOS/kg body weight/day, the highest test concentration. Based on this NOAEL and an estimate of consumption determined from the proposed inclusion of the beta-glucanase in feed at the maximum recommended level (426 U/kg), a margin of safety value of 5681 was calculated based on highest expected daily feed intake in broilers, the target species with highest feed intake relative to body weight. The findings support the safe use of beta-glucanase as an animal feed additive.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102125"},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044122","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 : 2025-09-05DOI: 10.1016/j.toxrep.2025.102124
Piper Reid Hunt, Nicholas Olejnik, Jeffrey Yourick, Robert L. Sprando
Developmental delay and spontaneous locomotor activity changes, as well as the reversibility of these adverse effects are apical endpoints used in chemical safety evaluations. These endpoints were assessed at sublethal concentrations in C. elegans using 5-fluorouracil (5FU), hydroxyurea (HU), or ribavirin (RV), teratogens that are associated with reduced fetal growth in mammals. C. elegans develop from egg to egg-laying adult in about three days. Synchronized cohorts were exposed either continuously, or for 24 h (early-only) from first-feeding after hatching. Developmental delays were dose-responsive for all three chemicals in both exposure schemes. For 5FU and HU, developmental delays and hypoactivity levels were similar in continuous and early-only exposure groups, consistent with irreversible developmental effects. The observed hypoactivity in developing C. elegans may be related to reported 5FU-induced muscle impairment and HU-induced post-exposure effects on locomotion parameters in mammals. In contrast to 5FU- and HU-induced hypoactivity, RV was associated with a non-significant trend to slight hyperactivity in both exposure schemes. Continuous RV exposures induced delays to sequential developmental milestones that increased with exposure duration. RV-induced delays were significantly reduced but not eliminated in early-only exposure cohorts, consistent with cumulative RV effects on developmental progress. These findings suggest that C. elegans may be a useful model for detecting chemicals with irreversible, reversible, and/or cumulative effects on organismal development.
{"title":"The Caenorhabditis elegans worm Development and Activity Test (wDAT) can be used to differentiate between reversible and irreversible developmental effects","authors":"Piper Reid Hunt, Nicholas Olejnik, Jeffrey Yourick, Robert L. Sprando","doi":"10.1016/j.toxrep.2025.102124","DOIUrl":"10.1016/j.toxrep.2025.102124","url":null,"abstract":"<div><div>Developmental delay and spontaneous locomotor activity changes, as well as the reversibility of these adverse effects are apical endpoints used in chemical safety evaluations. These endpoints were assessed at sublethal concentrations in <em>C. elegans</em> using 5-fluorouracil (5FU), hydroxyurea (HU), or ribavirin (RV), teratogens that are associated with reduced fetal growth in mammals. <em>C. elegans</em> develop from egg to egg-laying adult in about three days. Synchronized cohorts were exposed either continuously, or for 24 h (early-only) from first-feeding after hatching. Developmental delays were dose-responsive for all three chemicals in both exposure schemes. For 5FU and HU, developmental delays and hypoactivity levels were similar in continuous and early-only exposure groups, consistent with irreversible developmental effects. The observed hypoactivity in developing <em>C. elegans</em> may be related to reported 5FU-induced muscle impairment and HU-induced post-exposure effects on locomotion parameters in mammals. In contrast to 5FU- and HU-induced hypoactivity, RV was associated with a non-significant trend to slight hyperactivity in both exposure schemes. Continuous RV exposures induced delays to sequential developmental milestones that increased with exposure duration. RV-induced delays were significantly reduced but not eliminated in early-only exposure cohorts, consistent with cumulative RV effects on developmental progress. These findings suggest that <em>C. elegans</em> may be a useful model for detecting chemicals with irreversible, reversible, and/or cumulative effects on organismal development.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102124"},"PeriodicalIF":0.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004060","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}
This study aims to assess the exposure levels of Pb, Cd, and Cr and evaluate trends in heavy metal exposure among the population of Addis Ababa. A cross-sectional study was conducted involving 417 participants randomly selected from the population. Spot urine and water samples, socio-demographic characteristics, and food consumption frequency were collected. Heavy metals were analyzed using microwave plasma-atomic emission spectroscopy. Metal exposure risk from drinking water was assessed. The median concentrations of urinary Pb, Cr, and Cd were 19.4865 µg/g creatinine, 55.65 µg/g creatinine, and below the detection limit (Bd), respectively. Female participants and individuals who consumed meat daily had the highest median concentration of Pb (p < 0.005). Those who drank two or more cups of water daily had lower Pb (P < 0.01). Females who consumed eggs daily and drank two or more cups of water had the highest concentration of Cd, ranking in the 75th percentile. The median Cr concentration was higher in underweight participants (BMI < 18.5 kg/m²) at 88.41 µg/g creatinine and in overweight participants (BMI ≥ 25 kg/m²) at 66.49 µg/g creatinine compared to normal-weight participants, who had a median concentration of 48.44 µg/g creatinine (P < 0.01). Three metals were detected in 14.4 % and two metals in 52.8 %, and their levels showed an increasing trend over 12 years. Health risk analysis revealed that the highest Cumulative Incremental Life Cancer Risk (CILCR) values were found in Kirkos (KR-10–1.9 ×10−3), Lideta (LI-10–2.33 ×10−3), and Nifas Silk (NS-11–2.46 ×10−3) districts, indicating a significant cancer risk associated with cumulative exposure.
{"title":"Assessment of heavy metal exposure and cancer risk in Addis Ababa: Trends, risk factors and demographic variations in urinary cadmium, lead and chromium levels","authors":"Tsigereda Assefa Alemayehu , Andualem Mekonnen Hiruy , Mehari Meles , Belay Tefera , Tadesse Alemu Terfie","doi":"10.1016/j.toxrep.2025.102122","DOIUrl":"10.1016/j.toxrep.2025.102122","url":null,"abstract":"<div><div>This study aims to assess the exposure levels of Pb, Cd, and Cr and evaluate trends in heavy metal exposure among the population of Addis Ababa. A cross-sectional study was conducted involving 417 participants randomly selected from the population. Spot urine and water samples, socio-demographic characteristics, and food consumption frequency were collected. Heavy metals were analyzed using microwave plasma-atomic emission spectroscopy. Metal exposure risk from drinking water was assessed. The median concentrations of urinary Pb, Cr, and Cd were 19.4865 µg/g creatinine, 55.65 µg/g creatinine, and below the detection limit (Bd), respectively. Female participants and individuals who consumed meat daily had the highest median concentration of Pb (p < 0.005). Those who drank two or more cups of water daily had lower Pb (P < 0.01). Females who consumed eggs daily and drank two or more cups of water had the highest concentration of Cd, ranking in the 75th percentile. The median Cr concentration was higher in underweight participants (BMI < 18.5 kg/m²) at 88.41 µg/g creatinine and in overweight participants (BMI ≥ 25 kg/m²) at 66.49 µg/g creatinine compared to normal-weight participants, who had a median concentration of 48.44 µg/g creatinine (P < 0.01). Three metals were detected in 14.4 % and two metals in 52.8 %, and their levels showed an increasing trend over 12 years. Health risk analysis revealed that the highest Cumulative Incremental Life Cancer Risk (CILCR) values were found in Kirkos (KR-10–1.9 ×10<sup>−3</sup>), Lideta (LI-10–2.33 ×10<sup>−3</sup>), and Nifas Silk (NS-11–2.46 ×10<sup>−3</sup>) districts, indicating a significant cancer risk associated with cumulative exposure.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102122"},"PeriodicalIF":0.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996242","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 : 2025-09-02DOI: 10.1016/j.toxrep.2025.102123
Ali M. Al-Joda , Munaf H. Zalzala
Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with persistent inflammation, oxidative stress, and epithelial apoptosis. Nicardipine, a dihydropyridine calcium channel blocker, exhibits anti-inflammatory and anti-apoptotic properties, but its therapeutic potential in UC remains unclear. This study evaluated the effects of nicardipine on dextran sulfate sodium (DSS)-induced colitis in mice, focusing on inflammatory, oxidative, and apoptotic pathways. Fifty BALB/c mice were assigned to five groups (n = 10): control, DSS, nicardipine 12 mg/kg, nicardipine 24 mg/kg, and 5-aminosalicylate (ASA) 75 mg/kg. Treatments were administered for 3 days before and 10 days during DSS exposure. Disease severity was assessed by body weight, disease activity index (DAI), and colon length. Colonic mRNA levels of Nlrp3, TNF-α, IL-17, and TNFSF10 were quantified by RT-PCR; protein expression of caspase-3, caspase-8, BAX, and BCL-2 was analyzed by Western blot. Serum malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase-1 (GPX-1), occludin, and prostaglandin E₂ (PGE-2) were measured by ELISA. Histological scoring assessed epithelial integrity and inflammation. Nicardipine dose-dependently reduced DSS-induced weight loss, DAI, and colon shortening. Both doses significantly downregulated Nlrp3, TNF-α, IL-17, and TNFSF10 (p < 0.05), decreased caspase-3 and BAX, and increased BCL-2. Nicardipine restored GPX-1, lowered MDA and MPO, preserved occludin, and reduced PGE-2. Histology confirmed reduced mucosal injury and preserved epithelial architecture. Nicardipine attenuates DSS-induced colitis by suppressing pro-inflammatory cytokines, reducing oxidative stress, and inhibiting apoptosis, supporting its potential as a therapeutic candidate for UC. Further studies are warranted to clarify its molecular mechanisms and clinical relevance.
{"title":"The protective role of nicardipine in dextran sulfate sodium-induced colitis in mice: Modulating inflammation and apoptosis","authors":"Ali M. Al-Joda , Munaf H. Zalzala","doi":"10.1016/j.toxrep.2025.102123","DOIUrl":"10.1016/j.toxrep.2025.102123","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with persistent inflammation, oxidative stress, and epithelial apoptosis. Nicardipine, a dihydropyridine calcium channel blocker, exhibits anti-inflammatory and anti-apoptotic properties, but its therapeutic potential in UC remains unclear. This study evaluated the effects of nicardipine on dextran sulfate sodium (DSS)-induced colitis in mice, focusing on inflammatory, oxidative, and apoptotic pathways. Fifty BALB/c mice were assigned to five groups (n = 10): control, DSS, nicardipine 12 mg/kg, nicardipine 24 mg/kg, and 5-aminosalicylate (ASA) 75 mg/kg. Treatments were administered for 3 days before and 10 days during DSS exposure. Disease severity was assessed by body weight, disease activity index (DAI), and colon length. Colonic mRNA levels of <em>Nlrp3</em>, <em>TNF-α</em>, <em>IL-17, and TNFSF10 were quantified by RT-PCR; protein expression of caspase-3, caspase-8, BAX, and BCL-2</em> was analyzed by Western blot. Serum malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase-1 (GPX-1), occludin, and prostaglandin E₂ (PGE-2) were measured by ELISA. Histological scoring assessed epithelial integrity and inflammation. Nicardipine dose-dependently reduced DSS-induced weight loss, DAI, and colon shortening. Both doses significantly downregulated <em>Nlrp3</em>, <em>TNF-α</em>, <em>IL-17, and TNFSF10 (p < 0.05), decreased caspase-3 and BAX, and increased BCL-2</em>. Nicardipine restored GPX-1, lowered MDA and MPO, preserved occludin, and reduced PGE-2. Histology confirmed reduced mucosal injury and preserved epithelial architecture. Nicardipine attenuates DSS-induced colitis by suppressing pro-inflammatory cytokines, reducing oxidative stress, and inhibiting apoptosis, supporting its potential as a therapeutic candidate for UC. Further studies are warranted to clarify its molecular mechanisms and clinical relevance.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102123"},"PeriodicalIF":0.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019086","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}
Heavy metal contamination is a serious concern affecting the safety of tap water sources. Hence, this study evaluated physicochemical quality indices, carcinogenic and non-carcinogenic health hazard derived from the level of toxic metals in tap water in Gondar city, Ethiopia. The results revealed that except dissolved oxygen, salinity and nitrite, all quality attributes were below the allowable quality standards. The average concentrations for iron (Fe), copper (Cu), lead (Pb), chromium (Cr) and cadmium (Cd) were ranged from 0.003 mg/L to 5 mg/L, 0.475 mg/L to 0.752 mg/L, 0.14 mg/L to 0.703 mg/L, 0.261 mg/L to 2.182 mg/L, and 0.035 mg/L to 4.286 mg/L, respectively. The mean levels of metals in different areas decreased in the order: AR > AZ1 > PS1 > AZ3 > PS2 > MR > PS3 > SHD > AZ2 > CL. Except for Cu, the concentration of Fe, Pb, Cr, and Cd exceeded the safe limits described by WHO/FAO. According to principal component analysis and cluster analysis, anthropogenic activities were found to be the major source of metals. Chronic daily intake (CDI), target hazard quotient (THQ), hazard index (HI), and incremental lifetime cancer risk assessment (ILCR) were employed to evaluate human health risks. Except for Pb in AZ1, PS3, and AR, the values of THQ for both ingestion and dermal pathways from the analysed metals for adults were within the safety limits (THQ 1). However, the distribution pattern of HI values were presented in the decreasing order: PS1 > PS2 > AZ3 > MR > PS3 > AR > AZ2 > AZ1 > SHD > CL. Except, the HI values in CL, all values were greater than one (HI > 1), indicating that tap water in these areas may pose non-carcinogenic health risk. The analysis of carcinogenic health risks indicated that the lifetime cancer risk (ingestion and dermal exposure pathways) of heavy metals were in accordance with the acceptable range for tap water (10–6 – 10–4). This finding provides valuable input for the development of precise action plans aimed at elevating water quality standards in the studied areas.
{"title":"Holistic approach to assess human health risks, integrating physicochemical quality attributes and heavy metal levels in tap water","authors":"Molla Tefera , Habtamu Aderajew , Dessie Ezez , Mamo Dikamu , Worku Lakew","doi":"10.1016/j.toxrep.2025.102121","DOIUrl":"10.1016/j.toxrep.2025.102121","url":null,"abstract":"<div><div>Heavy metal contamination is a serious concern affecting the safety of tap water sources. Hence, this study evaluated physicochemical quality indices, carcinogenic and non-carcinogenic health hazard derived from the level of toxic metals in tap water in Gondar city, Ethiopia. The results revealed that except dissolved oxygen, salinity and nitrite, all quality attributes were below the allowable quality standards. The average concentrations for iron (Fe), copper (Cu), lead (Pb), chromium (Cr) and cadmium (Cd) were ranged from 0.003 mg/L to 5 mg/L, 0.475 mg/L to 0.752 mg/L, 0.14 mg/L to 0.703 mg/L, 0.261 mg/L to 2.182 mg/L, and 0.035 mg/L to 4.286 mg/L, respectively. The mean levels of metals in different areas decreased in the order: AR > AZ1 > PS1 > AZ3 > PS2 > MR > PS3 > SHD > AZ2 > CL. Except for Cu, the concentration of Fe, Pb, Cr, and Cd exceeded the safe limits described by WHO/FAO. According to principal component analysis and cluster analysis, anthropogenic activities were found to be the major source of metals. Chronic daily intake (CDI), target hazard quotient (THQ), hazard index (HI), and incremental lifetime cancer risk assessment (ILCR) were employed to evaluate human health risks. Except for Pb in AZ1, PS3, and AR, the values of THQ for both ingestion and dermal pathways from the analysed metals for adults were within the safety limits (THQ <span><math><mo><</mo></math></span>1). However, the distribution pattern of HI values were presented in the decreasing order: PS1 > PS2 > AZ3 > MR > PS3 > AR > AZ2 > AZ1 > SHD > CL. Except, the HI values in CL, all values were greater than one (HI > 1), indicating that tap water in these areas may pose non-carcinogenic health risk. The analysis of carcinogenic health risks indicated that the lifetime cancer risk (ingestion and dermal exposure pathways) of heavy metals were in accordance with the acceptable range for tap water (10<sup>–6</sup> – 10<sup>–4</sup>). This finding provides valuable input for the development of precise action plans aimed at elevating water quality standards in the studied areas.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102121"},"PeriodicalIF":0.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925002","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}
[This corrects the article DOI: 10.1016/j.toxrep.2025.102106.].
[这更正了文章DOI: 10.1016/j.toxrep.2025.102106.]。
{"title":"Corrigendum to: \"Delayed-onset status epilepticus without cholinergic features in organophosphate poisoning: A case report\" [Toxicol. Rep. 15 (2025) 102106].","authors":"Shayani Vimalanathan, Pramith Ruwanpathirana, Thashi Chang","doi":"10.1016/j.toxrep.2025.102118","DOIUrl":"https://doi.org/10.1016/j.toxrep.2025.102118","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.toxrep.2025.102106.].</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"102118"},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12745936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865342","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}
Pub Date : 2025-08-26DOI: 10.1016/j.toxrep.2025.102120
Ruaa Adnan Mohammed , Nada N. Al-Shawi
5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent, but its hepatotoxic potential poses clinical challenges, as it induces oxidative stress, inflammation, and apoptosis in liver tissue. Butein, a natural chalcone flavonoid that possesses varied biological activity, such as anticancer, anti-inflammatory, and antiplatelet effects. This study aimed to evaluate the possible protective effects of Butein against 5-FU-induced hepatotoxicity in rats. Male albino rats were divided into 4 Groups (of 7 animals each): control, 5-FU, and two Butein-pretreated Groups (50 and 100 mg/kg/day, orally for 14 days) each before a single intraperitoneal dose of 150 mg/kg 5-FU, which was injected on day 14. Serum liver enzymes (ALT and AST), cytokines (IL-6, IL-10, and NF-κB), oxidative stress markers (MDA and GSH), TNF-α gene expression, and protein levels of caspase-3 and NRF2 were evaluated. Histological assessments were also conducted. 5-FU significantly elevated serum ALT and AST levels, increased NF-κB, IL-6, MDA, and TNF-α expression, and decreased IL-10, GSH, and NRF2 levels (p < 0.05). Histological changes included sinusoidal dilation, congestion, and hepatocyte degeneration. Pre-treatment with Butein markedly attenuated these alterations, where both doses of Butein significantly reduced transaminases, pro-inflammatory cytokines, and oxidative stress markers while enhancing antioxidant defenses and anti-inflammatory IL-10 levels. Notably, the high dose of Butein restored NRF2 expression and reduced caspase-3 protein levels more effectively than the lower dose. Histologically, the high dose of Butein preserved normal hepatic architecture with minimal pathological changes. In conclusoin, Butein offers dose-dependent hepatoprotection against 5-FU-induced liver injury through the attenuation of oxidative stress, suppression of pro-inflammatory and apoptotic markers, and upregulation of antioxidant defenses; moreover, the histopathological evaluation further supported the biochemical and molecular findings, particularly at the 100 mg/kg/day, which preserved normal hepatic architecture and minimized cellular damage; and, thus support the prophylactic potentialof Butein in managing chemotherapeutic liver toxicity.
{"title":"Butein mitigates 5-FU-triggered hepatotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways","authors":"Ruaa Adnan Mohammed , Nada N. Al-Shawi","doi":"10.1016/j.toxrep.2025.102120","DOIUrl":"10.1016/j.toxrep.2025.102120","url":null,"abstract":"<div><div>5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent, but its hepatotoxic potential poses clinical challenges, as it induces oxidative stress, inflammation, and apoptosis in liver tissue. Butein, a natural chalcone flavonoid that possesses varied biological activity, such as anticancer, anti-inflammatory, and antiplatelet effects. This study aimed to evaluate the possible protective effects of Butein against 5-FU-induced hepatotoxicity in rats. Male albino rats were divided into 4 Groups (of 7 animals each): control, 5-FU, and two Butein-pretreated Groups (50 and 100 mg/kg/day, orally for 14 days) each before a single intraperitoneal dose of 150 mg/kg 5-FU, which was injected on day 14. Serum liver enzymes (ALT and AST), cytokines (IL-6, IL-10, and NF-κB), oxidative stress markers (MDA and GSH), TNF-α gene expression, and protein levels of caspase-3 and NRF2 were evaluated. Histological assessments were also conducted. 5-FU significantly elevated serum ALT and AST levels, increased NF-κB, IL-6, MDA, and TNF-α expression, and decreased IL-10, GSH, and NRF2 levels (p < 0.05). Histological changes included sinusoidal dilation, congestion, and hepatocyte degeneration. Pre-treatment with Butein markedly attenuated these alterations, where both doses of Butein significantly reduced transaminases, pro-inflammatory cytokines, and oxidative stress markers while enhancing antioxidant defenses and anti-inflammatory IL-10 levels. Notably, the high dose of Butein restored NRF2 expression and reduced caspase-3 protein levels more effectively than the lower dose. Histologically, the high dose of Butein preserved normal hepatic architecture with minimal pathological changes. In conclusoin, Butein offers dose-dependent hepatoprotection against 5-FU-induced liver injury through the attenuation of oxidative stress, suppression of pro-inflammatory and apoptotic markers, and upregulation of antioxidant defenses; moreover, the histopathological evaluation further supported the biochemical and molecular findings, particularly at the 100 mg/kg/day, which preserved normal hepatic architecture and minimized cellular damage; and, thus support the prophylactic potentialof Butein in managing chemotherapeutic liver toxicity.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102120"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912098","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}
The study examines the health of petroleum industry employees in Basrah City, southern Iraq, with a focus on their exposure to toxic chemicals, specifically the impact of oxidative stress on their hearts. This study included two groups of men: in the first group, ninety employees were exposed to crude oil well sites in Basrah, and ninety individuals were in the control group. This study evaluated two ultra-fine particles in the participants' blood: the polycyclic aromatic hydrocarbon metabolite [Benzopyrene diol epoxide (BPDE)] level and the toxic cadmium. The study also aimed to evaluate the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the serum of the study participants and monitor the lipid profile. The results showed high levels of BPDE, a high concentration of cadmium in the blood, increased lipid peroxidation, and decreased SOD in the exposed group compared to the control group. The results also showed a significant increase in triglycerides. The increase in reactive oxygen species production is a major risk factor for atherosclerosis, and high triglycerides indicate artery wall deposits, leading to cardiovascular disease.
{"title":"Clinical study on the relationship between exposure to ultrafine particles (PM0.1) and cardiovascular diseases in petroleum workers","authors":"Nagham Jawad Kadam AL-Lami , Nadhum A.N. Awad , Saad Shaheen Hamadi Al-Taher","doi":"10.1016/j.toxrep.2025.102119","DOIUrl":"10.1016/j.toxrep.2025.102119","url":null,"abstract":"<div><div>The study examines the health of petroleum industry employees in Basrah City, southern Iraq, with a focus on their exposure to toxic chemicals, specifically the impact of oxidative stress on their hearts. This study included two groups of men: in the first group, ninety employees were exposed to crude oil well sites in Basrah, and ninety individuals were in the control group. This study evaluated two ultra-fine particles in the participants' blood: the polycyclic aromatic hydrocarbon metabolite [Benzopyrene diol epoxide (BPDE)] level and the toxic cadmium. The study also aimed to evaluate the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the serum of the study participants and monitor the lipid profile. The results showed high levels of BPDE, a high concentration of cadmium in the blood, increased lipid peroxidation, and decreased SOD in the exposed group compared to the control group. The results also showed a significant increase in triglycerides. The increase in reactive oxygen species production is a major risk factor for atherosclerosis, and high triglycerides indicate artery wall deposits, leading to cardiovascular disease.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102119"},"PeriodicalIF":0.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988579","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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