Pub Date : 2025-12-01Epub Date: 2025-09-19DOI: 10.1016/j.toxrep.2025.102130
Matthew Elcombe, Stephanie Wallace, Simon Plummer
A key event in the process of rat but not human liver carcinogenesis caused by constitutive androstane receptor activators such as phenobarbital (PB) is hepatocyte proliferation, but the mechanism(s) underpinning this response is not fully understood. Previously we showed that rat liver microtissues (LiMTs) can recapitulate a PB-induced hepatocyte proliferation response (1). In this follow up study we used our microTMA technology coupled with transcriptomics and immunofluorescence (IF) staining to elucidate mechanisms of rat liver carcinogenesis in this model. We performed gene set enrichment analysis (GSEA) on transcriptomics data generated from laser microdissected liver microtissue microTMA FFPE sections from control and PB-treated LiMTs against custom liver cell proliferation and constitutive androstane receptor (CAR) activation signatures (2) and found that the former signature was significantly (q<0.25) enriched in rat but not human LiMT differentially expressed gene lists. This process also identified the cell proliferation gene nucleophosmin 1 (NPM1) as being significantly induced (p < 0.05) in rat but not human LiMTs. IF staining of parallel microTMA FFPE sections coupled with quantitative image analysis confirmed that the NPM1 protein was induced by PB treatment in rat but not human liver microtissues after 24 and 48 hrs PB treatment. In conclusion we have identified induction of nuclear NPM1 expression as an early event in PB-induced rat hepatocyte cell proliferation.
{"title":"Nucleophosmin 1 induction is an early event in a Phenobarbital induced proliferation response in rat but not human liver 3D microtissues","authors":"Matthew Elcombe, Stephanie Wallace, Simon Plummer","doi":"10.1016/j.toxrep.2025.102130","DOIUrl":"10.1016/j.toxrep.2025.102130","url":null,"abstract":"<div><div>A key event in the process of rat but not human liver carcinogenesis caused by constitutive androstane receptor activators such as phenobarbital (PB) is hepatocyte proliferation, but the mechanism(s) underpinning this response is not fully understood. Previously we showed that rat liver microtissues (LiMTs) can recapitulate a PB-induced hepatocyte proliferation response (1). In this follow up study we used our microTMA technology coupled with transcriptomics and immunofluorescence (IF) staining to elucidate mechanisms of rat liver carcinogenesis in this model. We performed gene set enrichment analysis (GSEA) on transcriptomics data generated from laser microdissected liver microtissue microTMA FFPE sections from control and PB-treated LiMTs against custom liver cell proliferation and constitutive androstane receptor (CAR) activation signatures (2) and found that the former signature was significantly (q<0.25) enriched in rat but not human LiMT differentially expressed gene lists. This process also identified the cell proliferation gene nucleophosmin 1 (NPM1) as being significantly induced (p < 0.05) in rat but not human LiMTs. IF staining of parallel microTMA FFPE sections coupled with quantitative image analysis confirmed that the NPM1 protein was induced by PB treatment in rat but not human liver microtissues after 24 and 48 hrs PB treatment. In conclusion we have identified induction of nuclear NPM1 expression as an early event in PB-induced rat hepatocyte cell proliferation.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102130"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117667","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 : 2025-12-01Epub 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":"2025-12-01","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 : 2025-12-01Epub Date: 2025-08-15DOI: 10.1016/j.toxrep.2025.102113
Daniel Itiza Akaahan , Augustine Uche Agu , Nkemjika Chinyere Anyanwu , Vivian Onyinye Orjiako , Godson Emeka Anyanwu
Background
Methylparaben is a commonly used preservative in the cosmetics, pharmaceutical, and food industries, valued for its antibacterial and antifungal effects. Numerous in vitro and in vivo studies have investigated its adverse effects on sperm count, testosterone levels, and reproductive organ weight. Baicalin, which comes from the dried roots of the plant Scutellaria baicalensis Georgi, is a natural compound that may have various health benefits, such as reducing fibrosis, itching, bacteria, oxidative stress, inflammation, and cancer. This study investigated the effect of baicalin on the changes in male reproductive hormones and enzyme activity brought about by methylparaben.
Method
A total of forty-five adult male Wistar rats were randomly allocated into nine distinct groups, each comprising five rats. Over a period of 28 days, these subjects were administered treatments via gastric gavage, which included distilled water, peanut oil, methylparaben, or differing doses of baicalin, either in isolation or in conjunction with methylparaben. Post-treatment, blood samples were obtained under terminal anesthesia for the purpose of serum analysis. Assays for hormonal levels (FSH, LH, testosterone) and enzymatic activity (17β-HSD3) were performed utilising ELISA and spectrophotometric techniques in accordance with established protocols.
Results
Rats treated with methylparaben (Group 3) had much lower levels of FSH, LH, testosterone, and 17β-HSD compared to the other groups, and baicalin was able to reduce these effects in a dose-dependent manner. Higher baicalin doses restored hormone and enzyme levels to near-control values levels indicating its protective benefits.
Conclusion
The results indicate that baicalin could mitigate the reproductive toxicity induced by methylparaben, owing to its antioxidant and regulatory characteristics, highlighting its potential as a protective agent against endocrine-disrupting chemicals
{"title":"Protective role of baicalin against methylparaben-induced reproductive toxicity: Insights into hormonal and enzymatic regulation","authors":"Daniel Itiza Akaahan , Augustine Uche Agu , Nkemjika Chinyere Anyanwu , Vivian Onyinye Orjiako , Godson Emeka Anyanwu","doi":"10.1016/j.toxrep.2025.102113","DOIUrl":"10.1016/j.toxrep.2025.102113","url":null,"abstract":"<div><h3>Background</h3><div>Methylparaben is a commonly used preservative in the cosmetics, pharmaceutical, and food industries, valued for its antibacterial and antifungal effects. Numerous in vitro and in vivo studies have investigated its adverse effects on sperm count, testosterone levels, and reproductive organ weight. Baicalin, which comes from the dried roots of the plant Scutellaria baicalensis Georgi, is a natural compound that may have various health benefits, such as reducing fibrosis, itching, bacteria, oxidative stress, inflammation, and cancer. This study investigated the effect of baicalin on the changes in male reproductive hormones and enzyme activity brought about by methylparaben.</div></div><div><h3>Method</h3><div>A total of forty-five adult male Wistar rats were randomly allocated into nine distinct groups, each comprising five rats. Over a period of 28 days, these subjects were administered treatments via gastric gavage, which included distilled water, peanut oil, methylparaben, or differing doses of baicalin, either in isolation or in conjunction with methylparaben. Post-treatment, blood samples were obtained under terminal anesthesia for the purpose of serum analysis. Assays for hormonal levels (FSH, LH, testosterone) and enzymatic activity (17β-HSD3) were performed utilising ELISA and spectrophotometric techniques in accordance with established protocols.</div></div><div><h3>Results</h3><div>Rats treated with methylparaben (Group 3) had much lower levels of FSH, LH, testosterone, and 17β-HSD compared to the other groups, and baicalin was able to reduce these effects in a dose-dependent manner. Higher baicalin doses restored hormone and enzyme levels to near-control values levels indicating its protective benefits.</div></div><div><h3>Conclusion</h3><div>The results indicate that baicalin could mitigate the reproductive toxicity induced by methylparaben, owing to its antioxidant and regulatory characteristics, highlighting its potential as a protective agent against endocrine-disrupting chemicals</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102113"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865711","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 : 2025-12-01Epub Date: 2025-07-30DOI: 10.1016/j.toxrep.2025.102095
Sarah Berlinski , Bruce Calder , Dennis Paustenbach
Winter gloves are often treated with fluoroacrylic surface coatings containing per- and polyfluoroalkyl substances (PFAS) to enhance water resistance. Concern over exposure to water-soluble PFAS, those with the greatest toxicological and regulatory relevance, has grown, particularly for children, who may experience higher relative body burdens due to lower body weight and frequent hand-to-mouth behaviors. In this study, we characterized the PFAS content and migration potential of winter gloves and conducted a screening-level risk assessment of perfluorooctanoic acid (PFOA) and perfluorohexanoic acid (PFHxA) glove exposures in children aged 2–6, considering both hand-to-mouth transfer and dermal absorption. Experimental data were generated through total fluorine analysis, liquid chromatography–tandem mass spectrometry (LC-MS/MS), gas chromatography–tandem mass spectrometry (GC-MS/MS), and leachate testing of individual glove components across eight glove brands. Three fluorotelomer compounds were detected above the limits of detection in 6 out of 173 components, spanning 3 of the 8 brands. No PFAS were detected in leachate samples, suggesting negligible migration under simulated use conditions. The calculated oral, dermal, and cumulative hazard indices, based on conservative, low-exposure scenarios using estimated concentrations below the detection limit, were all well below 0.001. This study contributes to the evidence base for PFAS risk assessment in consumer products and demonstrates that detectable PFAS residues do not necessarily translate to meaningful exposure or health risk. These findings support the use of risk-based regulatory approaches that incorporate realistic exposure scenarios in the evaluation of PFAS in treated textiles.
{"title":"An evaluation and risk assessment of children’s exposures to water-soluble per- and polyfluoroalkyl substances through winter gloves","authors":"Sarah Berlinski , Bruce Calder , Dennis Paustenbach","doi":"10.1016/j.toxrep.2025.102095","DOIUrl":"10.1016/j.toxrep.2025.102095","url":null,"abstract":"<div><div>Winter gloves are often treated with fluoroacrylic surface coatings containing per- and polyfluoroalkyl substances (PFAS) to enhance water resistance. Concern over exposure to water-soluble PFAS, those with the greatest toxicological and regulatory relevance, has grown, particularly for children, who may experience higher relative body burdens due to lower body weight and frequent hand-to-mouth behaviors. In this study, we characterized the PFAS content and migration potential of winter gloves and conducted a screening-level risk assessment of perfluorooctanoic acid (PFOA) and perfluorohexanoic acid (PFHxA) glove exposures in children aged 2–6, considering both hand-to-mouth transfer and dermal absorption. Experimental data were generated through total fluorine analysis, liquid chromatography–tandem mass spectrometry (LC-MS/MS), gas chromatography–tandem mass spectrometry (GC-MS/MS), and leachate testing of individual glove components across eight glove brands. Three fluorotelomer compounds were detected above the limits of detection in 6 out of 173 components, spanning 3 of the 8 brands. No PFAS were detected in leachate samples, suggesting negligible migration under simulated use conditions. The calculated oral, dermal, and cumulative hazard indices, based on conservative, low-exposure scenarios using estimated concentrations below the detection limit, were all well below 0.001. This study contributes to the evidence base for PFAS risk assessment in consumer products and demonstrates that detectable PFAS residues do not necessarily translate to meaningful exposure or health risk. These findings support the use of risk-based regulatory approaches that incorporate realistic exposure scenarios in the evaluation of PFAS in treated textiles.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102095"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895630","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}
Parkinson's disease (PD), a prevalent neurodegenerative disorder, is marked by dopaminergic neuron loss and motor impairments. This study aimed to establish and compare PD models in adult zebrafish using two neurotoxins, MPTP and rotenone, evaluating their impact on behaviour and histopathology. Zebrafish were exposed to MPTP via intraperitoneal injection at two different doses or to rotenone in water for 21 days. Behavioural assessments, including Novel Tank Diving Test, bradykinesia, and C-bend response, revealed progressive motor and anxiety-like impairments, with rotenone exhibiting stronger locomotor effects. Histopathological analyses confirmed dose-dependent neurodegeneration in brain regions, with MPTP showing localized damage and rotenone causing widespread but milder effects. While both neurotoxins induced PD-like phenotypes, rotenone produced more pronounced locomotor deficits, whereas MPTP triggered anxiety-like symptoms. In conclusion, our study demonstrates that MPTP induces significant locomotor dysfunction along with anxiety-like symptoms, while rotenone strongly impacts locomotion with mild anxiety effects. Both neurotoxins exhibited maximum effects at their highest doses and over a similar time frame (Day 14 to Day 22). These findings highlight the distinct neurotoxic mechanisms of MPTP and rotenone and their relevance in modelling PD pathogenesis. The zebrafish model provides a robust platform for studying neurodegenerative diseases and testing therapeutic interventions. Further studies are required to explore the molecular mechanisms underlying their neurotoxic effects and to validate these models for long-term and translational research.
{"title":"Comparative evaluation of MPTP and rotenone as inducing agents for Parkinson's disease in adult zebrafish: Behavioural and histopathological insights","authors":"Chetan Ashok , Naveen Kumar Rajasekaran , Srikanth Jeyabalan , Gayathri Veeraraghavan , Subalakshmi Suresh , Ramya Sugumar , Sugin Lal Jabaris , Vetriselvan Subramaniyan , Ling Shing Wong","doi":"10.1016/j.toxrep.2025.102084","DOIUrl":"10.1016/j.toxrep.2025.102084","url":null,"abstract":"<div><div>Parkinson's disease (PD), a prevalent neurodegenerative disorder, is marked by dopaminergic neuron loss and motor impairments. This study aimed to establish and compare PD models in adult zebrafish using two neurotoxins, MPTP and rotenone, evaluating their impact on behaviour and histopathology. Zebrafish were exposed to MPTP via intraperitoneal injection at two different doses or to rotenone in water for 21 days. Behavioural assessments, including Novel Tank Diving Test, bradykinesia, and C-bend response, revealed progressive motor and anxiety-like impairments, with rotenone exhibiting stronger locomotor effects. Histopathological analyses confirmed dose-dependent neurodegeneration in brain regions, with MPTP showing localized damage and rotenone causing widespread but milder effects. While both neurotoxins induced PD-like phenotypes, rotenone produced more pronounced locomotor deficits, whereas MPTP triggered anxiety-like symptoms. In conclusion, our study demonstrates that MPTP induces significant locomotor dysfunction along with anxiety-like symptoms, while rotenone strongly impacts locomotion with mild anxiety effects. Both neurotoxins exhibited maximum effects at their highest doses and over a similar time frame (Day 14 to Day 22). These findings highlight the distinct neurotoxic mechanisms of MPTP and rotenone and their relevance in modelling PD pathogenesis. The zebrafish model provides a robust platform for studying neurodegenerative diseases and testing therapeutic interventions. Further studies are required to explore the molecular mechanisms underlying their neurotoxic effects and to validate these models for long-term and translational research.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102084"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653162","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":"2025-12-01","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}
Pub Date : 2025-12-01Epub 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":"2025-12-01","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 : 2025-12-01Epub 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":"2025-12-01","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}
Pub Date : 2025-12-01Epub Date: 2025-10-14DOI: 10.1016/j.toxrep.2025.102142
Shamim Al Mamun , Jannatara Ferdush , Alisha Islam , Sowmik Das Sowmya , Brett H. Robinson , Ismail Rahman
Contamination of staple foods with potentially toxic elements (PTEs) poses significant health concerns. Following reports of elevated concentrations of cadmium (Cd), chromium (Cr), nickel (Ni), and lead (Pb) in Bangladeshi soils, we aimed to determine the concentrations of these elements in commonly consumed vegetables (n = 10 species) and rice (n = 5 varieties) collected from markets in the Jamalpur district, Bangladesh, a representative rural market, to evaluate the associated human health risks. Mean PTE concentrations in vegetables frequently exceeded FAO/WHO food safety standards (FSS). All rice samples exceeded the FSS limits for Cd, Ni, and Pb, with 80 % exceeding the Cr limits. Health risks were calculated using estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI), and target carcinogenic risk (TCR). While cumulative non-carcinogenic risks (HI < 1) were within acceptable levels for both adults and children, the EDI values for Cd, Ni, and Pb in adults, as well as Cd and Cr in children, exceeded their respective tolerable daily intakes (TDI). The TCR for Cd and Cr exceeded the USEPA threshold (10−4) for both age groups, indicating significant carcinogenic risks. Principal component analysis revealed that Cd, Ni, and Pb likely originated from common sources such as industrial emissions and contaminated irrigation water, while Cr appeared to stem from distinct inputs, possibly agrochemicals or textile-related activities. These findings indicate potential health risks, including carcinogenic effects, from dietary PTE exposure in Jamalpur. The results suggest that similar rural regions may benefit from source control, rigorous monitoring, and regulatory interventions to ensure food safety.
{"title":"Potentially toxic elements in the Bangladeshi diet: An assessment of plant-based foods from a rural market","authors":"Shamim Al Mamun , Jannatara Ferdush , Alisha Islam , Sowmik Das Sowmya , Brett H. Robinson , Ismail Rahman","doi":"10.1016/j.toxrep.2025.102142","DOIUrl":"10.1016/j.toxrep.2025.102142","url":null,"abstract":"<div><div>Contamination of staple foods with potentially toxic elements (PTEs) poses significant health concerns. Following reports of elevated concentrations of cadmium (Cd), chromium (Cr), nickel (Ni), and lead (Pb) in Bangladeshi soils, we aimed to determine the concentrations of these elements in commonly consumed vegetables (n = 10 species) and rice (n = 5 varieties) collected from markets in the Jamalpur district, Bangladesh, a representative rural market, to evaluate the associated human health risks. Mean PTE concentrations in vegetables frequently exceeded FAO/WHO food safety standards (FSS). All rice samples exceeded the FSS limits for Cd, Ni, and Pb, with 80 % exceeding the Cr limits. Health risks were calculated using estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI), and target carcinogenic risk (TCR). While cumulative non-carcinogenic risks (HI < 1) were within acceptable levels for both adults and children, the EDI values for Cd, Ni, and Pb in adults, as well as Cd and Cr in children, exceeded their respective tolerable daily intakes (TDI). The TCR for Cd and Cr exceeded the USEPA threshold (10<sup>−4</sup>) for both age groups, indicating significant carcinogenic risks. Principal component analysis revealed that Cd, Ni, and Pb likely originated from common sources such as industrial emissions and contaminated irrigation water, while Cr appeared to stem from distinct inputs, possibly agrochemicals or textile-related activities. These findings indicate potential health risks, including carcinogenic effects, from dietary PTE exposure in Jamalpur. The results suggest that similar rural regions may benefit from source control, rigorous monitoring, and regulatory interventions to ensure food safety.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102142"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575946","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 : 2025-12-01Epub Date: 2025-10-13DOI: 10.1016/j.toxrep.2025.102141
Cailey E. Dorman , Dimitrios G. Giarikos , Amy C. Hirons , Carys L. Mitchelmore , D. Abigail Renegar
Inorganic arsenic, specifically arsenate [As(V)] and arsenite [As(III)], disrupts physiological and biochemical processes in marine organisms, yet their specific impacts on coral reef species remain largely unstudied. This study is the first to assess the acute and subacute toxicity of arsenate [As(V)] and arsenite [As(III)] on two threatened scleractinian coral species, Acropora cervicornis and Orbicella faveolata. Using four 96-h static-renewal assays, corals were exposed to six treatments: five concentrations and a negative control with all concentrations being analytically verified. Toxicity was evaluated through three endpoints: mortality (LC50), coral condition (EC50), and photosynthetic efficiency (IC50). The LC50s were found to be 0.0365 mg L−1 As(V) and 0.111 mg L−1 As(III) for A. cervicornis and 0.315 mg L−1 As(V) and 0.235 mg L−1 As(III) for O. faveolata. Both species showed significant adverse effects across all subacute endpoints, with Orbicella faveolata significantly more sensitive to As(III), whereas A. cervicornis showed greater sensitivity to As(V). This challenges the prevailing assumption that As(III) is universally more toxic to marine taxa. Species sensitivity distributions found that the LC50 values for these corals were lower than previously reported marine organism’s LC50s, highlighting the heightened vulnerability of coral. These findings provide critical data for refining sediment quality guidelines and improving ecological risk assessments in arsenic-impacted reef environments.
{"title":"Acute toxicity of arsenate and arsenite in two scleractinian coral species: Acropora cervicornis and Orbicella faveolata","authors":"Cailey E. Dorman , Dimitrios G. Giarikos , Amy C. Hirons , Carys L. Mitchelmore , D. Abigail Renegar","doi":"10.1016/j.toxrep.2025.102141","DOIUrl":"10.1016/j.toxrep.2025.102141","url":null,"abstract":"<div><div>Inorganic arsenic, specifically arsenate [As(V)] and arsenite [As(III)], disrupts physiological and biochemical processes in marine organisms, yet their specific impacts on coral reef species remain largely unstudied. This study is the first to assess the acute and subacute toxicity of arsenate [As(V)] and arsenite [As(III)] on two threatened scleractinian coral species, <em>Acropora cervicornis</em> and <em>Orbicella faveolata</em>. Using four 96-h static-renewal assays, corals were exposed to six treatments: five concentrations and a negative control with all concentrations being analytically verified. Toxicity was evaluated through three endpoints: mortality (LC50), coral condition (EC50), and photosynthetic efficiency (IC50). The LC50s were found to be 0.0365 mg L<sup>−1</sup> As(V) and 0.111 mg L<sup>−1</sup> As(III) for <em>A. cervicornis</em> and 0.315 mg L<sup>−1</sup> As(V) and 0.235 mg L<sup>−1</sup> As(III) for <em>O. faveolata</em>. Both species showed significant adverse effects across all subacute endpoints, with <em>Orbicella faveolata</em> significantly more sensitive to As(III), whereas <em>A. cervicornis</em> showed greater sensitivity to As(V). This challenges the prevailing assumption that As(III) is universally more toxic to marine taxa. Species sensitivity distributions found that the LC50 values for these corals were lower than previously reported marine organism’s LC50s, highlighting the heightened vulnerability of coral. These findings provide critical data for refining sediment quality guidelines and improving ecological risk assessments in arsenic-impacted reef environments.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102141"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361062","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}