Regulatory Toxicology and Pharmacology最新文献_第6页

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

Letter to the editors regarding “Inter-laboratory validation of bioaccessibility testing for metals” by Henderson et al. (2014) 就 "金属的生物可及性测试的实验室间验证 "致编辑的信，作者：.

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-08-22 DOI: 10.1016/j.yrtph.2024.105688

P.E. Rasmussen, P. Huntsman, T.M. Singer, M.N. Jacobs, C.C. Trevithick-Sutton

引用次数: 0

Biomonitoring of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide: A global view 2,4-二氯苯氧乙酸（2,4-D）除草剂的生物监测：全球视野。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-08-19 DOI: 10.1016/j.yrtph.2024.105687

Denali Boon , Carol J. Burns

{"title":"Biomonitoring of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide: A global view","authors":"Denali Boon , Carol J. Burns","doi":"10.1016/j.yrtph.2024.105687","DOIUrl":"10.1016/j.yrtph.2024.105687","url":null,"abstract":"<div><p>We conducted a literature review of urinary 2,4-D in populations not associated with a herbicide application. Of the 33 studies identified, the median/mean concentrations were similar for children, adults, and pregnant women regardless of geography. Individuals with highest concentrations may have had opportunities to directly contact 2,4-D outside of an application. Most studies were conducted in populations in North America and did not examine potential sources of 2,4-D, or what factors might influence higher or lower urinary 2,4-D concentrations. In the future, prioritizing the examination of 2,4-D biomonitoring in other regions and collecting information on sources and factors influencing exposures would better our understanding of 2,4-D exposures globally. In all the studies reviewed the concentrations of urinary 2,4-D observed were orders of magnitude below the US regulatory endpoints, suggesting that people are not being exposed to 2,4-D at levels high enough to result in adverse health effects.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105687"},"PeriodicalIF":3.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001284/pdfft?md5=d176f9b39800327fd586b648c6567b0a&pid=1-s2.0-S0273230024001284-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018434","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

Prenatal developmental toxicity studies of allyl alcohol in rats and rabbits 工作标题：烯丙醇对大鼠和兔子的产前发育毒性研究。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-08-14 DOI: 10.1016/j.yrtph.2024.105684

Wade Barranco , Jefferson Fowles , Erik K. Rushton

{"title":"Prenatal developmental toxicity studies of allyl alcohol in rats and rabbits","authors":"Wade Barranco , Jefferson Fowles , Erik K. Rushton","doi":"10.1016/j.yrtph.2024.105684","DOIUrl":"10.1016/j.yrtph.2024.105684","url":null,"abstract":"<div><p>Allyl alcohol (C3H6O; prop-2-en-1-ol; CAS RN 107-18-6; EINECS 203-470-7) is used as an intermediate/monomer in polymerization reactions producing chemicals/optical resins or as a coupling/cross-linking agent for unsaturated polyester and alkyd resins. Human exposure to allyl alcohol (AA) is restricted to workplace manufacturing facilities where it is used in enclosed systems, which limits release and impact on environmental receptors. To address regulatory questions about possible developmental toxicity, two OECD Guideline studies were conducted. A rat developmental toxicity study found fetal and maternal toxicity, in the form of resorptions and decreased body weight and food consumption, but no teratogenic effects. A rabbit developmental toxicity study was subsequently conducted upon request by the European Chemical Agency in 2011 under the REACH program and likewise reported maternal toxicity in the form of reductions in body weight gain and food consumption, but neither fetal toxicity or teratogenic effects. The results of both studies are presented and compared in this paper. Based on our review of the collective results of these studies, AA is considered non-teratogenic, yet does elicit increased post-implantation loss and reduced fetal body weight, possibly resulting from concomitant maternal toxicity. Based on the results of these studies, a maternal and developmental toxicity No Observed Adverse Effect Level of 10 mg/kg/day was apparent for both species.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105684"},"PeriodicalIF":3.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996340","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