Regulatory Toxicology and Pharmacology最新文献_第4页

Regulatory safety evaluation of key lime (Citrus aurantiifolia) peel ethanol extract: Acute, 90-day repeated-dose, and genotoxicity studies 酸橙皮乙醇提取物的监管安全性评估：急性、90天重复剂量和遗传毒性研究。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-11-26 DOI: 10.1016/j.yrtph.2025.106005

Yunjin Choi , Seonghui Kim , Duhyeon Kim , Kyoung Sik Park , Mi-Young Lee , Suengmok Cho

{"title":"Regulatory safety evaluation of key lime (Citrus aurantiifolia) peel ethanol extract: Acute, 90-day repeated-dose, and genotoxicity studies","authors":"Yunjin Choi , Seonghui Kim , Duhyeon Kim , Kyoung Sik Park , Mi-Young Lee , Suengmok Cho","doi":"10.1016/j.yrtph.2025.106005","DOIUrl":"10.1016/j.yrtph.2025.106005","url":null,"abstract":"<div><div>Key lime (<em>Citrus aurantiifolia</em>) peel, a major by-product of juice processing, is rich in flavonoids and other bioactives. To support its safe use as a food-derived ingredient, we chemically characterized key lime peel ethanol extract (KLPE) and conducted a full toxicological evaluation under OECD Test Guidelines (No. 420, 408, 471, 473, 474) and in compliance with GLP. The program included acute oral toxicity, a 90-day repeated-dose study with a 28-day recovery, and in vitro and in vivo genotoxicity assays. KLPE caused no mortality or clinical signs, and body weight, food intake, hematology, and organ weights were comparable to controls. No histopathological lesions or genotoxic effects were observed. Both the LD<sub>50</sub> and the No Observed Adverse Effect Level (NOAEL) exceeded 2000 mg/kg BW/day, the highest dose tested, indicating a wide safety margin. These results provide regulatory-grade evidence confirming the safety of KLPE for human consumption and support its application as a functional food and nutraceutical ingredient in global markets.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"165 ","pages":"Article 106005"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145638124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Use of human data for risk assessment of pesticides: A review including an evaluation of trichlorfon as case study 使用人类数据进行农药风险评估：一项审查，包括对敌百虫作为个案研究的评价。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-12-09 DOI: 10.1016/j.yrtph.2025.106011

Giulia Collatuzzo , Paolo Boffetta

{"title":"Use of human data for risk assessment of pesticides: A review including an evaluation of trichlorfon as case study","authors":"Giulia Collatuzzo , Paolo Boffetta","doi":"10.1016/j.yrtph.2025.106011","DOIUrl":"10.1016/j.yrtph.2025.106011","url":null,"abstract":"<div><div>Pesticides are suspected to cause health effects in humans, but human-based data on their toxicity are often insufficient to establish associations and quantify risks. We reviewed literature on trichlorfon and investigated methodological aspects of risk assessment for pesticides based on human data. We provided an overview of epidemiology of pesticide toxicity, with focus on methodological features of the available studies, combined with a systematic review of the health effects of the pesticide, trichlorfon in humans, focusing on studies published after 1990. Studies on dichlorvos, the metabolite of trichlorfon, as well as metrifonate, a medication with the identical formula as trichlorfon, were included. A total of 60 publications were identified on health effects of trichlorfon, dichlorvos and metrifonate. Studies on acute effects (N = 23 publications) comprised mainly case-reports related to accidents and suicidal attempts, and were connoted by cholinergic syndrome, gastrointestinal and general symptoms. Evidence on chronic effects derived from analyses of the Agricultural Health Study (28 publications), as well as case-control and cross-sectional studies (9 publications). Evidence of possible associations between trichlorfon or dichlorvos exposure and various outcomes was heterogeneous and insufficient to establish causality. Critical features of epidemiology studies used for pesticide risk assessment include study design, exposure misclassification, lack of quantitative exposure data, and lack of consideration to potential confounders. Few high-quality epidemiology studies are available on potential health effects of trichlorfon. Future studies conducted according to established guidelines and supported by artificial intelligence might help to fill the gap on human health risks from pesticides.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"165 ","pages":"Article 106011"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Demonstration of safety for rice bran wax and sunflower wax based on bridging to other naturally derived waxes used in foods 米糠蜡和葵花蜡与食品中其他天然衍生蜡桥接的安全性论证。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-11-15 DOI: 10.1016/j.yrtph.2025.105990

N. Choksi , D. McMillan , D. Schmitt , C. Doepker , R.G. Henderson

{"title":"Demonstration of safety for rice bran wax and sunflower wax based on bridging to other naturally derived waxes used in foods","authors":"N. Choksi , D. McMillan , D. Schmitt , C. Doepker , R.G. Henderson","doi":"10.1016/j.yrtph.2025.105990","DOIUrl":"10.1016/j.yrtph.2025.105990","url":null,"abstract":"<div><div>Novel waxes require safety documentation, which traditionally involves using a battery of assays in experimental animals. For a class of well-studied substances (e.g., waxes) generally recognized to be of low or no toxicity, bridging methods that leverage safety information to fill data gaps for new substances may be considered. The aim of this assessment was to use a bridging assessment procedure to fill data gaps to demonstrate safety for two novel plant waxes (rice bran wax and sunflower wax). Using the European Chemicals Agency (ECHA) framework methodology, compositional similarity was established between the novel waxes and four well-evaluated plant waxes. Using the evidence bases for the evaluated plant waxes, the bridging assessment predicted that rice bran and sunflower waxes would have limited absorption. The bridging assessments also predicted that rice bran and sunflower waxes had limited repeat-dose oral toxicity, and were not reproductive or developmental toxicants or carcinogenic. Predicted lack of acute and mutagenic activity by rice bran wax was supported by experimental data. In conclusion, this case study shows that the bridging approach can fill toxicity data gaps, supporting a waiver of additional <em>in vivo</em> tests, thus ensuring safety, as well as reducing the use of animal testing.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"165 ","pages":"Article 105990"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145542065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of chronic toxicity and carcinogenicity of HFPO-DA in mice HFPO-DA对小鼠的慢性毒性和致癌性评价。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-12-13 DOI: 10.1016/j.yrtph.2025.106014

Chad M. Thompson , Melissa M. Heintz , John M. Cullen , Laurie C. Haws

{"title":"Evaluation of chronic toxicity and carcinogenicity of HFPO-DA in mice","authors":"Chad M. Thompson , Melissa M. Heintz , John M. Cullen , Laurie C. Haws","doi":"10.1016/j.yrtph.2025.106014","DOIUrl":"10.1016/j.yrtph.2025.106014","url":null,"abstract":"<div><div>Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (HFPO-DA; CAS#: 62037-80-3) was tested for potential toxicity and carcinogenicity in CD-1 mice administered 0, 0.05, 0.1, 0.5, or 5 mg/kg-day HFPO-DA via oral gavage for 9 or 18 months. Histopathological examinations were conducted at each time point along with clinical chemistry measurements. Reduced survival was observed in male mice exposed to 5 mg/kg-day for 18 months but not 9 months. Hepatocellular hypertrophy was the most sensitive histopathological response to HFPO-DA and was significantly increased in both sexes at 9 and 18 months of exposure. At 18 months, hepatocellular hypertrophy was not observed below 0.1 mg/kg-day. Liver tumors were significantly increased at 5 mg/kg-day in males at both timepoints and in females at 18 months. No other treatment related tumors were observed. Consistent with previously published studies in mice, transcriptomic responses in the liver of both sexes showed enrichment of peroxisome proliferator-activated receptor alpha (PPARα) signaling pathways. These changes demonstrate that the tumor response in the liver is consistent with a PPARα mode of action. Other noncancer histopathological effects were limited to the adrenal gland (5 mg/kg-day at ≥9 months) and testes (≥0.5 mg/kg-day at 18 months) of male mice.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"165 ","pages":"Article 106014"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ICH Q3C revisited part I: Evaluation of class 1 residual solvents ICH Q3C重访第1部分：1类残留溶剂的再评价

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-10-23 DOI: 10.1016/j.yrtph.2025.105970

David J. Snodin

引用次数: 0

Methoxyflurane exposure in ambulances: a controlled laboratory study on paramedic safety 救护车中甲氧基氟醚暴露：护理人员安全的对照实验室研究。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI: 10.1016/j.yrtph.2025.106012

Michael A. Austin , Somalin Mao , Jonathan MacLeod , Zachary Cantor

{"title":"Methoxyflurane exposure in ambulances: a controlled laboratory study on paramedic safety","authors":"Michael A. Austin , Somalin Mao , Jonathan MacLeod , Zachary Cantor","doi":"10.1016/j.yrtph.2025.106012","DOIUrl":"10.1016/j.yrtph.2025.106012","url":null,"abstract":"<div><div>Methoxyflurane, a self-administered fluorinated hydrocarbon, provides rapid, relief for traumatic pain. While low-dose methoxyflurane poses minimal risk, paramedics may experience intermittent exposure. This study assesses occupational risks to enhance paramedic safety, health standards, and patient care directives.</div><div>Active air sampling was conducted in a Ministry of Health-approved ambulance, in the driver and patient compartment, under controlled conditions, both with and without ventilation. Twelve healthy participants inhaled for 15 min, with samples collected per EPA and ISO standards. Results were adjusted for time weighted average (TWA) exposure.</div><div>Twenty-four air samples were collected (median age 30.5 years, 50 % female). Exposure concentrations remained below 8-h TWA occupational limits and NIOSH 60-min ceiling limits. With ventilation, 8-h TWA levels were 0.001 ppm (driver) and 0.033 ppm (patient compartment), rising to 0.017 ppm and 0.057 ppm without ventilation. Maximum TWA levels for 22 transports (30-min duration) reached 0.019 ppm (driver) and 0.736 ppm (patient) with ventilation, increasing to 0.377 ppm and 1.254 ppm without. These were based upon worst-case assumptions of 22 treatment and transport events, each lasting 30 min, over a 12 h work shift. Ventilation significantly reduced exposure, with 99.1 % protocol adherence and no adverse events.</div><div>This controlled study confirms methoxyflurane's safe use in ambulances with exposure well below safety thresholds. Ventilation minimizes potential risk(s), ensuring paramedic safety and uninterrupted pain management.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"165 ","pages":"Article 106012"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Current approaches to the interpretation of bioactivity data from a neural network formation assay to inform developmental neurotoxicity potential of chemical exposure 目前从神经网络形成分析中解释生物活性数据的方法，以告知化学暴露的发育神经毒性潜力。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-12-03 DOI: 10.1016/j.yrtph.2025.106008

Kelly E. Carstens, Timothy J. Shafer

引用次数: 0

Assessing carcinogenic outcomes following short-term exposure to potentially DNA-reactive drugs: Are available data sufficient to inform risk assessment? 评估短期暴露于潜在dna反应性药物后的致癌结果：现有数据是否足以为风险评估提供信息？

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-11-20 DOI: 10.1016/j.yrtph.2025.105993

Dayton M. Petibone , Jennifer M. Shemansky , Timothy W. Robison , Aisar H. Atrakchi , Robert H. Heflich

{"title":"Assessing carcinogenic outcomes following short-term exposure to potentially DNA-reactive drugs: Are available data sufficient to inform risk assessment?","authors":"Dayton M. Petibone , Jennifer M. Shemansky , Timothy W. Robison , Aisar H. Atrakchi , Robert H. Heflich","doi":"10.1016/j.yrtph.2025.105993","DOIUrl":"10.1016/j.yrtph.2025.105993","url":null,"abstract":"<div><div>Phase 1 clinical trial participants could potentially be exposed to significant health risks. Findings from a standard battery of genetic toxicology tests typically are the only data available to inform about cancer hazards at the initiation of clinical trials. Although uncommon, a question occasionally arises that is not clearly defined in current guidance: how many doses of an Ames-positive (potentially DNA-reactive) drug can be administered safely to healthy adult subjects during Phase 1 clinical trials? A literature survey was undertaken to identify information on carcinogenic risks from short-term exposures to Ames-positive agents, which might inform about administering an Ames-positive drug as a single dose or over a period of up to 14 days in healthy adult subjects. Limited information was identified on risk predictions for short-term exposures from modeling applications and from human studies, with more extensive data available using animal models. Relevant information on cancer outcomes following short-term exposures to Ames-positive agents suggest there is an increased cancer risk for administering even a single dose of an Ames-positive drug to healthy adult subjects. These findings indicate that Phase 1 studies with Ames-positive drug candidates should be exceedingly rare, and that additional mutagenicity testing should be performed before drug administration.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"165 ","pages":"Article 105993"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomonitoring arsenic exposure by ancestry: the healthy life in an urban setting (HELIUS) study 祖先对砷暴露的生物监测：城市环境中的健康生活（HELIUS）研究。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-11-19 DOI: 10.1016/j.yrtph.2025.105994

L.M. Brewster , A. Ishwardat , B.J. van den Born , M.M.A.L. Pelsers , H. Galenkamp , G.A. van Montfrans

{"title":"Biomonitoring arsenic exposure by ancestry: the healthy life in an urban setting (HELIUS) study","authors":"L.M. Brewster , A. Ishwardat , B.J. van den Born , M.M.A.L. Pelsers , H. Galenkamp , G.A. van Montfrans","doi":"10.1016/j.yrtph.2025.105994","DOIUrl":"10.1016/j.yrtph.2025.105994","url":null,"abstract":"<div><div>Policymakers in Europe utilize biomonitoring to regulate exposure to arsenic and protect public health, but potentially high exposure levels among ancestral subgroups remain understudied.</div><div>We assessed arsenic exposure in a random population sample of Amsterdam, the Netherlands, stratified by European-Dutch vs Asian and African-Dutch ancestry (n = 60, 30 women, aged 40–63 years). We analyzed total spot urinary arsenic with inductively coupled plasma mass spectrometry and used food frequency questionnaires to calculate the exposure to inorganic arsenic (reference point <0.8 nmol/kg body mass/day) from rice, fish, and water consumption.</div><div>Urinary arsenic (40–4828 nmol/L, mean 532 (SE 116); respectively 312 (60) in European-Dutch vs. 642 (169) in Asian and African-Dutch), was independently associated with rice consumption (343 nmol/L (95 % CI, 112–575)/100 g rice).</div><div>Inorganic arsenic intake (87–976 nmol/day, mean 397, SE 32), respectively 175 (14) in European-Dutch (2.4 (0.2) nmol/kg body mass/day) vs 508 (37) in Asian and African-Dutch (6.7 (0.5) nmol/kg body mass/day), was independently associated with systolic blood pressure (3.1 (1.5–4.8) mm Hg/100 nmol iAs).</div><div>The high dietary arsenic exposure among certain ancestry subgroups living in Europe is concerning. Health policies should be developed to monitor these subgroups and reduce their inorganic arsenic intake to the unavoidable minimum.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"165 ","pages":"Article 105994"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction notice to“Safety evaluation and risk assessment of the herbicide roundup and its active ingredient, glyphosate, for humans” [Regul. Toxicol. Pharm. 31 (2000) 117–165] 关于“除草剂农达及其活性成分草甘膦对人类的安全性评估和风险评估”的撤回通知[法规]。Toxicol。医药，31(2000)117-165]。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-02-01 Epub Date: 2025-12-05 DOI: 10.1016/j.yrtph.2025.106006

Gary M. Williams , Robert Kroes , Ian C. Munro

引用次数: 0