Regulatory Toxicology and Pharmacology最新文献_第8页

The new paradigm in animal testing – “3Rs alternatives” 动物试验的新典范--"3Rs 替代品"。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-20 DOI: 10.1016/j.yrtph.2024.105705

Wen Tsin Poh, Johnson Stanslas

{"title":"The new paradigm in animal testing – “3Rs alternatives”","authors":"Wen Tsin Poh, Johnson Stanslas","doi":"10.1016/j.yrtph.2024.105705","DOIUrl":"10.1016/j.yrtph.2024.105705","url":null,"abstract":"<div><div>Regulatory studies have revolutionised over time. Today, the focus has shifted from animal toxicity testing to non-animal for regulatory safety testing. This move is in line with the international 3Rs (Replacement, Reduction, and Refinement) principle and has also changed the regulator's perspective. The 3R principle has stimulated changes in policy, regulations, and new approaches to safety assessment in drug development in many countries. The 3Rs approach has led to the discovery and application of new technologies and more human-relevant <em>in vitro</em> approaches that minimise the use of animals including non-human primates, in research and improve animal welfare. In 2016, the European Medicines Agency published the Guidelines on the principles of regulatory acceptance of 3Rs testing approaches, followed by a conceptual paper in 2023 to align with current 3R standards. Additionally, the United States Food and Drug Administration passed new legislation in 2023 that no longer requires all new human drugs to be tested on animals, which will change the current testing paradigm. This review paper provides the adoption of the 3Rs and the current regulatory perspective regarding their implementation.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105705"},"PeriodicalIF":3.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294042","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

Botanical-induced toxicity: Liver injury and botanical-drug interactions. A report on a society of Toxicology Annual Meeting symposium 植物药引起的毒性：肝损伤和植物药与药物的相互作用毒理学会年会专题讨论会报告。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-19 DOI: 10.1016/j.yrtph.2024.105708

Igor Koturbash , R. Philip Yeager , Constance A. Mitchell , Stephen Ferguson , Victor J. Navarro , Mary F. Paine , Amy L. Roe

{"title":"Botanical-induced toxicity: Liver injury and botanical-drug interactions. A report on a society of Toxicology Annual Meeting symposium","authors":"Igor Koturbash , R. Philip Yeager , Constance A. Mitchell , Stephen Ferguson , Victor J. Navarro , Mary F. Paine , Amy L. Roe","doi":"10.1016/j.yrtph.2024.105708","DOIUrl":"10.1016/j.yrtph.2024.105708","url":null,"abstract":"<div><div>Botanical supplements and herbal products are widely used by consumers for various purported health benefits, and their popularity is increasing. Some of these natural products can have adverse effects on liver function and/or interact with prescription and over-the-counter (OTC) medications. Ensuring the safety of these readily available products is a crucial public health concern; however, not all regulatory authorities require premarket safety review and/or testing. To address and discuss these and other emerging needs related to botanical safety, a symposium was held at the Society of Toxicology Annual Meeting in Salt Lake City (UT) on March 11, 2024. The symposium addressed the latest research on botanical-induced liver toxicity and botanical-drug interactions, including new approach methods to screen for toxicity, challenges in assessing the safety of botanicals, and relating human adverse events to specific products. The presentations and robust panel discussion between the speakers and audience highlighted the need for further research and collaboration to improve the safety of botanical supplements and herbal products, with the ultimate goal of protecting consumer health. Although utility of many of the modern tools presented in the symposium requires further study, the synergistic efforts of diverse experts hold promise for effective prediction and evaluation of botanical-induced hepatotoxicity and botanical-drug interaction potential.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105708"},"PeriodicalIF":3.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001491/pdfft?md5=b5bac393db266260b93676b9c48f5214&pid=1-s2.0-S0273230024001491-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Residue depletion profiles and withdrawal intervals of florfenicol and its metabolite florfenicol amine in plasma and milk of lactating goats after repeated subcutaneous administrations 重复皮下注射后哺乳山羊血浆和乳汁中氟苯尼考及其代谢物氟苯尼考胺的残留消耗曲线和停药间隔时间。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-18 DOI: 10.1016/j.yrtph.2024.105707

Qiran Chen , Zhoumeng Lin , Jennifer L. Davis , Emily Toney , Maaike O. Clapham , Xue Wu , Lisa A. Tell

{"title":"Residue depletion profiles and withdrawal intervals of florfenicol and its metabolite florfenicol amine in plasma and milk of lactating goats after repeated subcutaneous administrations","authors":"Qiran Chen , Zhoumeng Lin , Jennifer L. Davis , Emily Toney , Maaike O. Clapham , Xue Wu , Lisa A. Tell","doi":"10.1016/j.yrtph.2024.105707","DOIUrl":"10.1016/j.yrtph.2024.105707","url":null,"abstract":"<div><div>Florfenicol is a broad-spectrum and bacteriostatic antibiotic with a time-dependent killing action. It is commonly used to treat respiratory diseases in goats in an extra-label manner. This study aimed to determine the plasma pharmacokinetics and milk residue depletion profiles and calculate the milk withdrawal interval (WDI) of florfenicol and its main metabolite florfenicol amine in lactating goats. Five healthy lactating goats were administered with 40 mg/kg florfenicol by subcutaneous injection, twice, 96 h apart. Plasma and milk samples were collected up to 864 h post the first injection. Non-compartmental analysis was used to estimate the plasma pharmacokinetic parameters. Milk WDIs were calculated using the U.S. Food and Drug Administration (FDA) method and European Medicines Agency (EMA) method. A Monte Carlo simulation was performed to generate simulated data for five virtual animals to meet the data requirement of the FDA method. The calculated milk WDIs based on florfenicol, florfenicol amine, and the combined (the sum of florfenicol and florfenicol amine) were 720.28, 690.45, and 872.69 h after the last injection using the FDA method. In conclusion, this study improves our understanding on the plasma pharmacokinetics and milk residue depletion kinetics of florfenicol and florfenicol amine in lactating ruminants after subcutaneous injections.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105707"},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294041","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

Neurobehavioral assessment of BMEDA by modified Irwin test in Sprague-Dawley rats 通过改良欧文试验对 Sprague-Dawley 大鼠进行 BMEDA 神经行为评估。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-17 DOI: 10.1016/j.yrtph.2024.105703

Liang-Cheng Chen, Te-Wei Lee, Chih-Hsien Chang

{"title":"Neurobehavioral assessment of BMEDA by modified Irwin test in Sprague-Dawley rats","authors":"Liang-Cheng Chen, Te-Wei Lee, Chih-Hsien Chang","doi":"10.1016/j.yrtph.2024.105703","DOIUrl":"10.1016/j.yrtph.2024.105703","url":null,"abstract":"<div><div>The neurobehavioral assessment of N,N-bis(2-mercapatoethly)-N′,N′-diethylenediamine (BMEDA), which can form a chelate with rhenium-188 (<sup>188</sup>Re) to produce the <sup>188</sup>Re-BMEDA-liposome, was evaluated. The purpose of this study was to evaluate the potential neurobehavioral changes by using the functional observational battery observation procedures when intravenous injection of BMEDA to Sprague-Dawley rats. Rats were administered BMEDA at dose levels of 1, 2, and 5 mg/kg. No mortalities were observed. There are some observations related to BMEDA treatment found in the 5 mg/kg dose group at 10 min post-dose. Tremor was observed in one male rat and seven female rats. The increased respiration, vocalization, not easy to handle and/or loss of tone in the limb were observed in both males and females, and increased body temperature was observed in male animals. Based on the results, a single intravenous dose of BMEDA administered to rats resulted in increased respiration, vocalization, not easy to handle and/or loss of tone in the limb increasing at the dose level of 5 mg/kg. No neurobehavioral effects were noted after BMEDA administration up to the dose level of 2 mg/kg. The information of this study will provides a point of reference to design appropriately therapeutic studies for future human use.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105703"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294040","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

Building knowledge of NAMs through risk science 评论：通过风险科学积累非杀伤人员地雷知识。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-16 DOI: 10.1016/j.yrtph.2024.105702

Yadvinder Bhuller , Morgan Gale , Fevrelyn Yadao , Daniel Krewski

引用次数: 0

Reevaluating safety pharmacology respiratory studies within the ICH S7A core battery: A multi-company evaluation of preclinical utility and clinical translation 重新评估 ICH S7A 核心电池中的安全药理学呼吸研究：临床前实用性和临床转化的多公司评估。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-16 DOI: 10.1016/j.yrtph.2024.105706

G.S. Friedrichs , M.M. Abernathy , D. Ackley , M. Clark , J.K. DaSilva , C.M. Foley , A. Greiter-Wilke , K.A Henderson , J.J. Kremer , B.H. Morimoto , S. Paglialunga , M.K. Pugsley , C.P. Regan , E.I. Rossman , J.A. Segretti , M. Traebert , H.M. Vargas , T.A. Wisialowski

{"title":"Reevaluating safety pharmacology respiratory studies within the ICH S7A core battery: A multi-company evaluation of preclinical utility and clinical translation","authors":"G.S. Friedrichs , M.M. Abernathy , D. Ackley , M. Clark , J.K. DaSilva , C.M. Foley , A. Greiter-Wilke , K.A Henderson , J.J. Kremer , B.H. Morimoto , S. Paglialunga , M.K. Pugsley , C.P. Regan , E.I. Rossman , J.A. Segretti , M. Traebert , H.M. Vargas , T.A. Wisialowski","doi":"10.1016/j.yrtph.2024.105706","DOIUrl":"10.1016/j.yrtph.2024.105706","url":null,"abstract":"<div><div>Optimization of ICH safety guideline studies for inclusion into regulatory submissions is critical for resource conservation, animal use reduction, and efficient drug development. The ICH S7A guidance for Safety Pharmacology (SP) studies adopted in 2001 identified the core battery of studies to evaluate the acute safety of putative pharmaceutical molecules prior to First in Human (FIH) trials. To assess the utility of respiratory studies in predicting clinical AE's, seven pharmaceutical companies pooled preclinical and clinical respiratory findings. A large database of novel molecules included all relevant data from standard S7A respiratory (n = 459) and FIH studies (n = 309). The data were analyzed with respect to the progression of these molecules, clinical adverse event reporting of these same molecules, and achieved exposures. These S7A respiratory assay findings had no impact on compound progression, and only 12 of 309 drug candidates were ‘positive’ preclinically and reported a respiratory-related AE in clinical trials (i.e. cough, dyspnea, etc.), an overall incidence rate of 3.9%. Contingency tables/statistics support a lack of concordance of these preclinical assays. Overall, our extensive analysis clearly indicated that the preclinical respiratory assay fails to provide any prognostic value for detecting clinically relevant respiratory adverse events.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105706"},"PeriodicalIF":3.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267285","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

PBPK modeling demonstrates that exposure time adjustment is unnecessary for setting an acute manganese inhalation exposure guideline PBPK 模型表明，在制定急性锰吸入暴露指南时，无需对暴露时间进行调整

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-07 DOI: 10.1016/j.yrtph.2024.105698

Camarie S. Perry , Ann H. Verwiel , Tammie R. Covington , Deborah M. Proctor

引用次数: 0

Food for thought — Paving the way for a UK roadmap towards optimum consumer safety: Development, Endorsement and Regulatory acceptance of New Approach Methodologies (NAMs) in Chemical Risk Assessment and Beyond 启发思考--为英国实现最佳消费者安全路线图铺平道路：化学品风险评估及其他领域新方法 (NAM) 的开发、认可和监管验收。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-07 DOI: 10.1016/j.yrtph.2024.105701

Olivia J. Osborne , Phil Botham , Cath Mulholland , Claire Potter , David Gott , Amie Adkin , Alan Boobis

{"title":"Food for thought — Paving the way for a UK roadmap towards optimum consumer safety: Development, Endorsement and Regulatory acceptance of New Approach Methodologies (NAMs) in Chemical Risk Assessment and Beyond","authors":"Olivia J. Osborne , Phil Botham , Cath Mulholland , Claire Potter , David Gott , Amie Adkin , Alan Boobis","doi":"10.1016/j.yrtph.2024.105701","DOIUrl":"10.1016/j.yrtph.2024.105701","url":null,"abstract":"<div><p>Advances in biosciences, chemistry, technology, and computer sciences have resulted in the unparalleled development of candidate New Approach Methodologies over the last few years. Many of these are potentially invaluable in the safety assessment of chemicals, but very few have been adopted for regulatory decision making. There is an immediate opportunity to use NAMs in safety assessment where the vision is to be able to predict risk more rapidly, accurately, and efficiently to further assure consumer safety.</p><p>In order to achieve this, the UK Food Standards Agency (FSA) and the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) have developed a roadmap towards acceptance and integration of these new approach methodologies into safety and risk assessments for regulatory decision making. The roadmap provides a UK blueprint for the transition of NAMs from the research laboratory to their use in regulatory decision making. This will require close collaboration across disciplines (chemists, toxicologists, informaticians, risk assessors and others), and across chemical sectors, to develop, verify and utilise appropriate models. Linking up internationally, and harmonization will be fundamental.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105701"},"PeriodicalIF":3.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185703","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

Safety assessment of protein A and derivation of a parenteral health-based exposure limit 蛋白质 A 的安全性评估和基于健康的肠道外接触限值的推导。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-06 DOI: 10.1016/j.yrtph.2024.105700

Jessica C. Graham , Sathanandam S. Anand , Joel Bercu , Lauren Besenhofer , Christina de Zafra , Yu Feng , Craig Fisher , Jedd Hillegass , Richard Hutchinson , Robert Jolly , Chandrika Moudgal , Tyler Nicholas , Daniela Olszova , Matthew Schmitz , Florian Semmelmann

{"title":"Safety assessment of protein A and derivation of a parenteral health-based exposure limit","authors":"Jessica C. Graham , Sathanandam S. Anand , Joel Bercu , Lauren Besenhofer , Christina de Zafra , Yu Feng , Craig Fisher , Jedd Hillegass , Richard Hutchinson , Robert Jolly , Chandrika Moudgal , Tyler Nicholas , Daniela Olszova , Matthew Schmitz , Florian Semmelmann","doi":"10.1016/j.yrtph.2024.105700","DOIUrl":"10.1016/j.yrtph.2024.105700","url":null,"abstract":"<div><p>Protein A (PA) is a bacterial cell wall component of <em>Staphylococcus aureus</em> whose function is to bind to Immunoglobulin G (IgG). Given its ability to bind IgG as well as its stability and resistance to harsh acidic and basic cleaning conditions, it is commonly used in the affinity chromotography purification of biotherapeutics. This use can result in levels of PA being present in a drug product and subsequent patient exposure. Interestingly, PA was previously evaluated in clinical trials as well as supporting nonclinical studies, resulting in a database that enables the derivation of a health-based exposure limit (HBEL). Given the widespread use of PA in the pharmaceutical industry, the IQ DruSafe Impurities Safety Working Group (WG) evaluated the available information with the purpose of establishing a harmonized parenteral HBEL for PA. Based on this thorough, collaborative evaluation of nonclinical and clinical data available for PA, a parenteral HBEL of 1.2 μg/kg/dose (60 μg/dose for a 50 kg individual) is expected to be health protective for patients when it is present as an impurity in a biotherapeutic.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105700"},"PeriodicalIF":3.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001417/pdfft?md5=e9e00f0477df6a426fc85be9c4a3c5c1&pid=1-s2.0-S0273230024001417-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aspects of complexity in quality and safety assessment of peptide therapeutics and peptide-related impurities. A regulatory perspective 多肽疗法和多肽相关杂质质量与安全评估的复杂性。监管视角。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-06 DOI: 10.1016/j.yrtph.2024.105699

Cristiano Colalto

{"title":"Aspects of complexity in quality and safety assessment of peptide therapeutics and peptide-related impurities. A regulatory perspective","authors":"Cristiano Colalto","doi":"10.1016/j.yrtph.2024.105699","DOIUrl":"10.1016/j.yrtph.2024.105699","url":null,"abstract":"<div><p>In recent years, a number of therapeutic peptides have been authorized in the EU market, and several others are in the clinical development phase or under assessment for full dossier or generic applications. Quality and safety guidelines specific to peptides are limited, and some aspects have to be considered. In particular, concerns relate to the analytical investigation for impurities and the toxicological assessment of these substances. The guidelines and the compendial pharmacopoeias provide certain references but that may be questionable if interpreted according to whether therapeutic peptides are considered chemical or biological entities, large or small. The characterization of peptide-related impurities cannot follow the small molecule approach but should consider aspects closely linked to the complex mechanisms of action that these large molecules can exert in the human body. Although direct genotoxic mechanisms cannot be excluded, hazardous interactions on biological systems cannot be ruled out, as in the case of natural peptide toxins and their specific interactions with cellular or membrane targets. From a regulatory perspective, only after specific risk identification and characterization should an equally specific safety threshold in relation to potential toxicity be defined.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105699"},"PeriodicalIF":3.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146104","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