Toxicologic Pathology最新文献_第4页

Corrigendum to Toxicologic Pathology Forum: Opinion on Performing Good Laboratory Practice Histopathology Evaluation for Nonclinical Toxicity Studies in a Remote Location. 毒理学病理学论坛的更正：关于在偏远地区进行非临床毒性研究的良好实验室规范组织病理学评估的意见。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2025-03-18 DOI: 10.1177/01926233251322124

引用次数: 0

Toxicologic Pathology Forum*: Opinion on Assessing and Communicating Adversity for Implantable Medical Devices. 毒理病理学论坛*：关于评估和通报植入式医疗器械不良反应的意见。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2024-11-27 DOI: 10.1177/01926233241300313

L M Wancket, B Bolon, K A Funk, J C L Schuh

{"title":"Toxicologic Pathology Forum*: Opinion on Assessing and Communicating Adversity for Implantable Medical Devices.","authors":"L M Wancket, B Bolon, K A Funk, J C L Schuh","doi":"10.1177/01926233241300313","DOIUrl":"10.1177/01926233241300313","url":null,"abstract":"Medical devices are a product class encompassing many materials and intended uses. While adversity determination is a key part of nonclinical safety assessments, relatively little has been published about the unique challenges encountered when determining adversity for implantable medical devices. The current paper uses the Society of Toxicologic Pathology (STP)'s \"Scientific and Regulatory Policy Committee Recommended ('Best') Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies,\" which were crafted for conventional bio/pharmaceutical products (small and large molecules, cell and gene therapies, etc), as a framework for making adversity decisions for medical devices. Some best principles are directly translatable to medical devices: (1) adversity indicates harm to the animal; (2) effects should be assessed on their merits without speculation regarding future or unmeasured implications; (3) adversity decisions apply only to the test species under the specific conditions of the nonclinical study; and (4) adversity decisions and supporting evidence should be clearly stated in reports. However, unique considerations also apply for evaluating implanted medical devices, including testing of multiple articles in the same animal and the unavoidable tissue trauma during device implantation. This opinion piece offers suggestions for applying previously published STP best practice recommendations for assigning adversity to implantable medical devices.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"278-286"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740628","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

Scientific and Regulatory Policy Committee Points to Consider: Proposal and Recommendations to Reduce Euthanasia of Control Nonhuman Primates in Nonclinical Toxicity Studies. 科学和监管政策委员会指出：在非临床毒性研究中减少控制非人类灵长类动物安乐死的提案和建议。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2025-01-29 DOI: 10.1177/01926233241309905

Magali Guffroy, Tara Arndt, Erio Barale-Thomas, Susan Bolin, Armelle Grevot, Joelle Ibanes, Steven T Laing, Michael W Leach, Mandy Meindel, Xavier Palazzi, Lila Ramaiah, Julie Schwartz, Robert L Johnson

{"title":"Scientific and Regulatory Policy Committee Points to Consider: Proposal and Recommendations to Reduce Euthanasia of Control Nonhuman Primates in Nonclinical Toxicity Studies.","authors":"Magali Guffroy, Tara Arndt, Erio Barale-Thomas, Susan Bolin, Armelle Grevot, Joelle Ibanes, Steven T Laing, Michael W Leach, Mandy Meindel, Xavier Palazzi, Lila Ramaiah, Julie Schwartz, Robert L Johnson","doi":"10.1177/01926233241309905","DOIUrl":"10.1177/01926233241309905","url":null,"abstract":"Nonhuman primates (NHPs) have been and remain a highly valuable animal model with an essential role in translational research and pharmaceutical drug development. Based on current regulatory guidelines, the nonclinical safety of novel therapeutics should be evaluated in relevant nonclinical species, which commonly includes NHPs for biotherapeutics. Given the practical and ethical limitations on availability and/or use of NHPs and in line with the widely accepted guiding \"3Rs\" (replace, reduce, and refine) principles, many approaches have been considered to optimize toxicity study designs to meaningfully reduce the number of NHPs used. Standard general toxicity studies usually include four groups of equal size, including one group of vehicle control animals. Here, we describe an approach to achieve an overall significant reduction in control animal use, while also resolving many of the issues that may limit application of fully virtual control animals. We propose in Good Laboratory Practice (GLP)-compliant toxicity studies to maintain concurrent control group animals for the in-life phase of the studies, but to limit euthanasia to a subset of control animals. The nonterminated control animals can then be returned to the facility colony for reuse in subsequent studies. The proposed study design could lead to a 15% to 20% reduction in NHP usage. The scientific, logistical, and animal welfare considerations associated with such an approach and suggested solutions are discussed in detail.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"287-296"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068139","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

Development of a Deep Learning Tool to Support the Assessment of Thyroid Follicular Cell Hypertrophy in the Rat. 一种支持大鼠甲状腺滤泡细胞肥大评估的深度学习工具的开发。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2025-01-17 DOI: 10.1177/01926233241309328

Stuart W Naylor, Elizabeth F McInnes, James Alibhai, Scott Burgess, James Baily

{"title":"Development of a Deep Learning Tool to Support the Assessment of Thyroid Follicular Cell Hypertrophy in the Rat.","authors":"Stuart W Naylor, Elizabeth F McInnes, James Alibhai, Scott Burgess, James Baily","doi":"10.1177/01926233241309328","DOIUrl":"10.1177/01926233241309328","url":null,"abstract":"Thyroid tissue is sensitive to the effects of endocrine disrupting substances, and this represents a significant health concern. Histopathological analysis of tissue sections of the rat thyroid gland remains the gold standard for the evaluation for agrochemical effects on the thyroid. However, there is a high degree of variability in the appearance of the rat thyroid gland, and toxicologic pathologists often struggle to decide on and consistently apply a threshold for recording low-grade thyroid follicular hypertrophy. This research project developed a deep learning image analysis solution that provides a quantitative score based on the morphological measurements of individual follicles that can be integrated into the standard pathology workflow. To achieve this, a U-Net convolutional deep learning neural network was used that not just identifies the various tissue components but also delineates individual follicles. Further steps to process the raw individual follicle data were developed using empirical models optimized to produce thyroid activity scores that were shown to be superior to the mean epithelial area approach when compared with pathologists' scores. These scores can be used for pathologist decision support using appropriate statistical methods to assess the presence or absence of low-grade thyroid hypertrophy at the group level.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"240-250"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011957","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

Characterization of Pulmonary Pathology in the Golden Syrian Hamster Model of COVID-19 Using Micro-Computed Tomography. 用显微计算机断层扫描表征金叙利亚仓鼠新冠肺炎模型的肺部病理。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2024-12-05 DOI: 10.1177/01926233241300451

Julita A Ramirez, Micah D Dunlap, Reyna Prosnitz, Anderson Watson, Mary K Montgomery, Matthew Gutman, Timothy M Coskran, Samantha L Levinson, Katharine Yang, Isis Kanevsky, Shambhunath Choudhary

{"title":"Characterization of Pulmonary Pathology in the Golden Syrian Hamster Model of COVID-19 Using Micro-Computed Tomography.","authors":"Julita A Ramirez, Micah D Dunlap, Reyna Prosnitz, Anderson Watson, Mary K Montgomery, Matthew Gutman, Timothy M Coskran, Samantha L Levinson, Katharine Yang, Isis Kanevsky, Shambhunath Choudhary","doi":"10.1177/01926233241300451","DOIUrl":"10.1177/01926233241300451","url":null,"abstract":"The Golden Syrian hamster is a well-characterized rodent model for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-associated pneumonia. We sought to characterize the pulmonary disease course during SARS-CoV-2 infection (strain USA-WA1/2020) in the hamster model using micro-computed tomography (micro-CT) and compare radiologic observations with histopathologic findings. We observed a range of radiologic abnormalities, including ground glass opacities (GGOs), consolidations, air bronchograms, and pneumomediastinum. The appearance, distribution, and progression of these abnormalities in hamsters were similar to those observed in the lungs of coronavirus disease 2019 (COVID-19) patients by clinical CT and chest X-rays, and correlated with clinical signs and weight loss during the course of disease. Histopathological analysis of infected hamsters revealed lung pathology characteristic of COVID-19 pneumonia, and we observed a strong association between CT and histopathologic scorings. We also analyzed accumulation of air in the thoracic cavity by both manual and automated threshold-based segmentation and found that automated analysis significantly decreases the time needed for data analysis. Data presented here demonstrate that micro-CT imaging can be a major tool in preclinical investigative studies using animal models by providing early and detailed assessment of disease severity and outcomes.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"267-277"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781005","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

Toxicologic Pathology Forum: Opinion on Digital Primary Read and Peer Review-Diving Head-First Into the Deep Digital Pool! 毒理病理学论坛：关于数字化初读和同行评审的意见--一头扎进数字化深潭！

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-02-01 Epub Date: 2024-12-12 DOI: 10.1177/01926233241303909

Krista M D La Perle

引用次数: 0

Toxicologic Pathology Forum: Opinion on Digital Primary Read and Peer Review-Are We There Yet? 毒理学病理学论坛：对数字化初级阅读和同行评议的看法——我们到了吗？

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-02-01 Epub Date: 2025-01-18 DOI: 10.1177/01926233241303911

Kenneth A Schafer, Deepa B Rao

引用次数: 0

Historical Control Data of Spontaneous Lesions of Laboratory New Zealand White and Dutch Belted Rabbits (Oryctolagus Cuniculus) Used in Toxicity Studies. 用于毒性研究的实验室新西兰白兔和荷兰带兔自发病变的历史对照数据。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-02-01 Epub Date: 2025-01-26 DOI: 10.1177/01926233241298567

Davide Corbetta, Kaori Isobe, Romaisa Masood, Petrina Rogerson, Alys Bradley

{"title":"Historical Control Data of Spontaneous Lesions of Laboratory New Zealand White and Dutch Belted Rabbits (Oryctolagus Cuniculus) Used in Toxicity Studies.","authors":"Davide Corbetta, Kaori Isobe, Romaisa Masood, Petrina Rogerson, Alys Bradley","doi":"10.1177/01926233241298567","DOIUrl":"10.1177/01926233241298567","url":null,"abstract":"A retrospective study was performed to determine the incidences of spontaneous findings in control laboratory New Zealand White (NZW) and Dutch Belted (DB) rabbits. Terminal body and organ weights data were also collected. A total of 2170 NZW (526 males/1644 females), 100 DB rabbits (50 animals per sex), aged 4- to 7-month-old were obtained from 158 non-clinical studies evaluated between 2013 and 2022. The NZW rabbits had greater mean terminal body weights than DB strain. Mixed cell infiltration in the lung was the most recorded finding in both strains, followed by pulmonary inflammation/mononuclear cell infiltration. Differentiation between pulmonary \"infiltration\"/\"inflammation\" remained challenging as interpretation of guidelines for diagnostic terminology may vary amongst pathologists. Other common findings included mineralization and basophilia of the renal tubules; hepatic/renal mononuclear cell infiltration, all more common in females. Cysts were commonly recorded, with high prevalence in the oviduct, thyroid gland, ovary in NZW strain, while uterine, pituitary gland, and thyroid gland cysts were the most identified in DB rabbits. Neoplasms and infectious etiologies were absent. Most of the animals were sexually mature. To our knowledge, this is the most recent comprehensive study of spontaneous lesions and organ weights in both rabbit strains and should facilitate the differentiation of spontaneous and induced lesions in safety studies.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"187-209"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047917","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

Opinion on the Importance of Sharing Toxicologic Pathology Data for Educational and/or Scientific Purposes. 关于为教育和/或科学目的共享毒理病理学数据的重要性的意见。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-02-01 Epub Date: 2024-11-18 DOI: 10.1177/01926233241296122

Eveline de Rijk, Phaedra Cole, Anna-Lena Frisk, Frederic Gervais, Joost Lensen, Barbara Lenz, Lars Mecklenburg, Flavia Pasello Dos Santos, Annette Romeike, Catherine Ross

{"title":"Opinion on the Importance of Sharing Toxicologic Pathology Data for Educational and/or Scientific Purposes.","authors":"Eveline de Rijk, Phaedra Cole, Anna-Lena Frisk, Frederic Gervais, Joost Lensen, Barbara Lenz, Lars Mecklenburg, Flavia Pasello Dos Santos, Annette Romeike, Catherine Ross","doi":"10.1177/01926233241296122","DOIUrl":"10.1177/01926233241296122","url":null,"abstract":"Sharing pathology data is critical for educational and scientific purposes. Since most pharmaceutical or (agro)chemical companies outsource nonclinical safety assessment studies to contract research organizations (CROs), the pathology data of those studies are not owned by the investigator but is the legal property of the respective company sponsoring the work. Although some companies have installed policies that govern sharing of pathology data, many companies generally do not allow the external use of data by either the CRO-based study pathologist or the sponsor pathologist. Policies for governing the external use of data vary significantly. In this article, we present an overview of the different approaches taken across different companies (CROs, pharmaceutical/chemical companies, or other institutes) for sharing pathology material for educational and/or scientific purposes. The results of a survey and interviews with legal departments of different companies will be presented (anonymously) and discussed. In addition, the importance of sharing pathology data is addressed, as well as the challenges and opportunities this presents. Suggestions will be provided regarding what material should be made available and what will be needed to achieve agreement for this to happen.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"218-229"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669315","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

IHI VICT3R: Developing and Implementing Virtual Control Groups to Reduce Animal Use in Toxicology Research. 开发和实施虚拟控制组以减少毒理学研究中动物的使用。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-02-01 Epub Date: 2024-12-12 DOI: 10.1177/01926233241303906

Thomas Steger-Hartmann, Ferran Sanz, Frank Bringezu, Inari Soininen

{"title":"IHI VICT3R: Developing and Implementing Virtual Control Groups to Reduce Animal Use in Toxicology Research.","authors":"Thomas Steger-Hartmann, Ferran Sanz, Frank Bringezu, Inari Soininen","doi":"10.1177/01926233241303906","DOIUrl":"10.1177/01926233241303906","url":null,"abstract":"The virtual control group (VCG) concept was originally developed in the IMI2 project eTRANSAFE, using data of control animals which pharmaceutical companies have accrued over decades from animal toxicity studies. This control data could be repurposed to create virtual control animals to reduce or replace concurrent controls in animal studies. Initial work demonstrated the general feasibility of the VCG concept, but implementation requires significant further collaborative efforts. The new Innovative Health Initiative (IHI) project VICT3R aims to address these challenges and to obtain regulatory acceptance for the VCG concept. To achieve these goals, VICT3R will build a database comprising high-quality, standardized, and duly annotated control animal data from past and forthcoming toxicity studies. The VICT3R project will create workflows and computational tools to generate adequate VCGs based on statistical and artificial intelligence (AI) approaches. The validity, reproducibility, and robustness of the resulting VCGs will be assessed by comparing the performance of their use with that of real control groups.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"230-233"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814225","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