Toxicology Reports最新文献

{"title":"Acute recreational drug and ethanol poisoning among adolescents: An observational study from Oslo, Norway 2014–2023","authors":"Ingrid M. Stenbeck ,&nbsp;Lüsette A. Subi ,&nbsp;Mette Brekke ,&nbsp;Odd Martin Vallersnes","doi":"10.1016/j.toxrep.2025.102134","DOIUrl":"10.1016/j.toxrep.2025.102134","url":null,"abstract":"<div><h3>Aims</h3><div>To keep track on trends and changes over time, we describe drugs taken, clinical course, and incidence of recreational drug and ethanol poisoning among adolescents in Oslo, Norway, from 2014 to 2023.</div></div><div><h3>Methods</h3><div>We included all patients ≤ 20 years presenting to the city’s main emergency primary care clinic with recreational drug poisoning in 2014–2023, from 2018 also including sole ethanol poisoning. Data were retrospectively collected from local patient records. Incidences were estimated per 1000 inhabitants in Oslo aged 10–20 years per year.</div></div><div><h3>Results</h3><div>There were 1209 recreational drug poisonings, 51.1 % among girls. Cannabis was taken in 37.1 % of the cases, benzodiazepines in 22.2 %, heroin in 17.1 %, cocaine in 14.6 %, amphetamine in 13.1 %, and methylenedioxymethamphetamine (MDMA) in 12.2 %. More than one drug was taken in 406 (33.6 %) cases. There were 1675 sole ethanol poisonings, 59.9 % among girls. During the pandemic years 2020 and 2021 there was a temporary decrease in the incidence of sole ethanol poisoning, accompanied by an increase in recreational drug poisoning. Otherwise, the incidences were stable, except a marked increase for recreational drugs in 2023: recreational drug poisoning 1.20 (95 % CI 0.97–1.50) in 2014 and 3.55 (3.16–3.99) in 2023; sole ethanol poisoning 3.94 (3.50–4.42) in 2018 and 3.96 (3.54–4.42) in 2023. The incidence of recreational drug poisoning among girls were lower than among boys early in the study period, but higher from 2021.</div></div><div><h3>Conclusions</h3><div>Recreational drug poisoning in Oslo among adolescents was dominated by ethanol, cannabis, benzodiazepines, and heroin.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102134"},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219503","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}

{"title":"Building a predictive model for polycyclic aromatic hydrocarbon dosimetry in organotypically cultured human bronchial epithelial cells using benzo[a]pyrene","authors":"Victoria C. Colvin ,&nbsp;Kelley M. Bastin ,&nbsp;Lisbeth K. Siddens ,&nbsp;Monica L. Vermillion Maier ,&nbsp;David E. Williams ,&nbsp;Jordan N. Smith ,&nbsp;Susan C. Tilton","doi":"10.1016/j.toxrep.2025.102133","DOIUrl":"10.1016/j.toxrep.2025.102133","url":null,"abstract":"<div><div>The airway epithelium is a primary route of exposure for inhaled toxicants, and organotypic culture models represent an important advancement for toxicity testing compared to simple <em>in vitro</em> models that may lack metabolic capability and multicellular structure/communication associated with the bronchial epithelium <em>in vivo</em>. A quantitative understanding of chemical dosimetry is key for interpreting and extrapolating study results; however, dosimetry is understudied in organotypic models limiting ability to predict toxicity. We developed a dosimetry model for primary human bronchial epithelial cells (HBECs) cultured at the air-liquid interface (ALI) using benzo[<em>a</em>]pyrene (BAP), a representative polycyclic aromatic hydrocarbon. Dose and time course evaluation of metabolite formation and enzyme activity and expression were utilized to parameterize a cellular dosimetry model to improve the utility of ALI-HBECs for assessing chemical risk. Dosimetry analysis demonstrated absorption of BAP into cells and an increase in Phase 1 and 2 metabolites over time that correlated with regulation of metabolizing enzymes. BAP was cleared from cells by 48 h after exposure, and the primary metabolites generated in ALI-HBECs were BAP-3-phenol, BAP-4,5-dihydrodiol, BAP-7,8-dihydrodiol, BAP-9,10-dihydrodiol, BAP-7,8,9,10-tetrol, BAP-3-phenol-glucuronide, BAP-4,5-dihydrodiol-glucuronide, and BAP-9,10-dihydrodiol-glucuronide. The resulting dosimetry model described BAP and 7,8-dihydrodiol toxicokinetics in ALI-HBECs and suggested active excretion of 7,8-dihydrodiol. Overall, this study demonstrates metabolic competency of ALI-HBECs for BAP metabolism, demonstrates the usefulness of complex <em>in vitro</em> systems for human-relevant toxicity data, and exhibits how <em>in silico</em> models can be utilized for understanding the dosimetry of test compounds to aid in <em>in vitro</em> to human extrapolation of toxicity data for risk assessments.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102133"},"PeriodicalIF":0.0,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219502","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}

{"title":"Prolonged intermittent hemodialysis using a standard dialysate flow rate for severe overdose of sustained-release valproic acid: A case report","authors":"Hiroki Inoue ,&nbsp;Satoshi Yoshikawa ,&nbsp;Nobuyasu Matsukawa,&nbsp;Atsushi Shima ,&nbsp;Takuya Nishizawa ,&nbsp;Takeshi Ueda","doi":"10.1016/j.toxrep.2025.102132","DOIUrl":"10.1016/j.toxrep.2025.102132","url":null,"abstract":"<div><h3>Background</h3><div>Valproic acid poisoning can be life threatening and may require urgent extracorporeal elimination. In particular, sustained-release formulations pose a challenge, as conventional short-duration intermittent hemodialysis may fail to remove the drug sufficiently because of delayed and prolonged drug absorption. While prolonged intermittent hemodialysis is a rational alternative, its clinical effectiveness and safety in cases of severe sustained-release sodium valproate overdose have not been reported.</div></div><div><h3>Case</h3><div>A woman in her 20 s developed coma after ingesting 45 g (approximately 1100 mg/kg) of sustained-release VPA. Prolonged IHD was delivered for 22 h using a blood flow rate (Qb) of 180 mL/min and a dialysate flow rate (Qd) of 500 mL/min. Her consciousness improved in parallel with a marked decline in serum VPA levels, and she was discharged without any neurological sequelae. A two-point, on-dialysis apparent elimination half-life was estimated to be approximately 2.35 h.</div></div><div><h3>Conclusion</h3><div>In this case, prolonged IHD appeared to have an effect in decreasing VPA concentrations and was safely implemented with monitoring.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102132"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219501","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}

{"title":"Assessment of the main signaling pathways involved in the combined therapy of hepatocellular carcinoma using Sorafenib and NK cells in xenograft mice model","authors":"Faezeh Hosseinzadeh ,&nbsp;Tahereh Komeili movahhed ,&nbsp;Masoumeh Dolati ,&nbsp;Amir Hossein Kheirkhah ,&nbsp;Nima Beheshtizadeh ,&nbsp;Javad Verdi","doi":"10.1016/j.toxrep.2025.102131","DOIUrl":"10.1016/j.toxrep.2025.102131","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Sorafenib is the only FDA approved drug for HCC patients, affecting patient survival by just a few months with significant toxicities in approximately half of HCC patients and the poor prognosis of these patients. Thus, the combination therapy with Sorafenib and Natural killer (NK) cells has been suggested, due to NK cells' distinct effectiveness against HCC. This research examined the main signaling pathways in HCC progression affected by Sorafenib or NK cells in combination or individual treatment. The xenograft model of HCC was created by implanting human HepG2 cells subcutaneously into the flank of 12 nude mice and then divided into four groups: Control, Sorafenib, NK cells, and Sorafenib plus NK cells. Four weeks post tumor implantation, the mice were euthanized, and the levels of liver and kidney enzymes were analysed for safety purposes. Quantitative real-time PCR analysis was used to measure the expression of key effector genes related to Sorafenib and NK cell functions with focused on the signaling pathways involved in the development of HCC. The levels of Aspartate aminotransferase (AST), Alanine transaminase (ALT), Blood urea nitrogen (BUN), and creatinine (Cr) in all groups remained in normal ranges. The expression levels of certain proliferative, anti-apoptotic factors were reduced in groups treated with either Sorafenib or NK cells only, but in combinational treated group showed no significant differences compared to control group. Also, the NK cell effector function related genes were upregulated in NK cell treated group, but inhibited in co administration of both NK cell and Sorafenib. Therefore, combining Sorafenib and NK cells at the prescribed dosage led to a decrease in the anti-cancer efficiency of both and may not be a successful option for HCC treatment.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102131"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117665","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}

{"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,&nbsp;Stephanie Wallace,&nbsp;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&lt;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 &lt; 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":"2025-09-19","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}

{"title":"Subchronic oral toxicity and in vitro anti-neuroinflammatory evaluation of Ficus erecta leaves extract for potential functional food applications","authors":"Eunjin Sohn,&nbsp;Yu Jin Kim,&nbsp;Woo-Young Jeon,&nbsp;Sae-Rom Yoo,&nbsp;Kyuhyung Jo,&nbsp;Ami Lee,&nbsp;Aejin Kim,&nbsp;Jin Ah Ryuk,&nbsp;Chan-Sik Kim,&nbsp;Bu-Yeo Kim,&nbsp;Mee-Young Lee,&nbsp;Hye-Sun Lim,&nbsp;Youn-Hwan Hwang,&nbsp;Soo-Jin Jeong","doi":"10.1016/j.toxrep.2025.102129","DOIUrl":"10.1016/j.toxrep.2025.102129","url":null,"abstract":"<div><div><em>Ficus erecta</em> leaves, a traditional medicinal plant that is widely used in East Asia, have demonstrated promising cognitive-enhancing effects. However, the safety of its long-term administration has not been elucidated. Therefore, we evaluated the subchronic toxicity of an ethanol extract of <em>F. erecta</em> leaves (EEFE) by conducting 13-week repeated oral toxicity study using Sprague–Dawley (SD) rats. Male and female rats were administered EEFE at doses of 0, 500, 1000, or 2000 mg/kg/day. Clinical signs, body weight, food consumption, hematology, serum biochemistry, organ weights, and gross necropsy findings were also monitored. No treatment-related mortality or toxic effects were observed at any doses of EEFE. Accordingly, the No Observed Adverse Effect Level (NOAEL) was determined to be 2000 mg/kg/day for both sexes. Additionally, we observed anti-neuroinflammatory effects of EEFE and its active compound rutin in BV-2 microglia. EEFE and rutin significantly inhibited nitrate and prostaglandin E2 (PGE₂) production in BV-2 cells. These results support the safety and anti-inflammatory action of EEFE for further development as a candidate herbal therapeutic or functional food for improving cognitive health and age-related conditions.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102129"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117666","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}

{"title":"A case report of a 79-year-old female with aluminum toxicity presenting with altered mental status in Eldoret, Kenya","authors":"Ann Mutugi ,&nbsp;Eduardo Cadore Guzzo ,&nbsp;Matthew Koech ,&nbsp;Maritim Koech ,&nbsp;Jie Tang","doi":"10.1016/j.toxrep.2025.102128","DOIUrl":"10.1016/j.toxrep.2025.102128","url":null,"abstract":"<div><h3>Introduction</h3><div>Aluminum is renally excreted and can cause toxicity in patients with end-stage renal disease (ESRD). In low- and middle-income countries (LMICs), potential sources of aluminum toxicity include the use of aluminum cookware and clay pots, well water, and contaminated dialysis water.</div></div><div><h3>Patient concerns</h3><div>We report a case of an elderly East African woman from a rural area with ESRD who was undergoing twice-weekly hemodialysis and who presented with altered mental status. Acute cardiac and neurological events were ruled out. A head CT scan was normal. Both the infectious and metabolic workups were unremarkable. Since the patient came from a rural home where her family used clay pots, aluminum utensils, and well water for drinking, a decision was made to rule out aluminum toxicity. Serum aluminum levels were significantly elevated at 534 micrograms/L.</div></div><div><h3>Diagnosis</h3><div>Aluminum toxicity based on the clinical presentation and elevated serum aluminum levels</div></div><div><h3>Interventions</h3><div>Daily hemodialysis with a high-flux dialyzer. Deferoxamine was not administered because of concerns about life-threatening neurotoxicity.</div></div><div><h3>Outcomes</h3><div>Her mental status started to improve within a week of initiating intensified hemodialysis. After nine months, her serum aluminum level decreased by more than 50 %, and the patient’s cognition returned to her baseline.</div></div><div><h3>Take-home lessons</h3><div>ESRD patients in LMICs are at greater risk for potential aluminum toxicity than are those in developed countries. Regular testing of serum aluminum levels is necessary in these patients since the initial presentation of aluminum toxicity can be nonspecific.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102128"},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104775","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}

{"title":"Surviving cyanide poisoning: A case report highlighting the role of early antidote use","authors":"Berber C. Hospes ,&nbsp;Elise M.A. Slob ,&nbsp;Tom K. Brinkman ,&nbsp;Sharif M. Pasha ,&nbsp;Erik B. Wilms ,&nbsp;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}

{"title":"Safety evaluation of a fungal beta-glucanase","authors":"Dnyaneshwar Jondhale ,&nbsp;Corrine Harris ,&nbsp;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}

{"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,&nbsp;Nicholas Olejnik,&nbsp;Jeffrey Yourick,&nbsp;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}