-
Next-Generation Sequencing-Based Identification of Enterobacter hormaechei as Causative Agent of High Mortality Disease in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) Mice Toxicol. Pathol. (IF 1.5) Pub Date : 2024-03-13 Catherine Si, Kourtney Nickerson, Taylor Simmons, Parker Denton, M. Russell Nichols, Robert C. Dysko, Mark Hoenerhoff, Rinosh Mani, Cheryl Woods, Kenneth S. Henderson, Zachary T. Freeman
NOD.Cg- Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice, lacking many components of a mature immune system, are at increased risk of disease. General understanding of potential pathogens of these mice is limited. We describe a high mortality disease outbreak caused by an opportunistic bacterial infection in NSG mice. Affected animals exhibited perianal fecal staining, dehydration, and wasting. Histopathologic
-
Deep Learning–Based Spermatogenic Staging in Tissue Sections of Cynomolgus Macaque Testes Toxicol. Pathol. (IF 1.5) Pub Date : 2024-03-11 Lars Mecklenburg, C. Marc Luetjens, Annette Romeike, Rohit Garg, Pranab Samanta, Amogh Mohanty, Tijo Thomas, Gerhard Weinbauer
The indirect assessment of adverse effects on fertility in cynomolgus monkeys requires that tissue sections of the testis be microscopically evaluated with awareness of the stage of spermatogenesis that a particular cross-section of a seminiferous tubule is in. This difficult and subjective task could very much benefit from automation. Using digital whole slide images (WSIs) from tissue sections of
-
-
-
Proceedings of the 2023 Division of Translational Toxicology Satellite Symposium Toxicol. Pathol. (IF 1.5) Pub Date : 2024-03-06 Erin M. Quist, Ronnie Chamanza, Amanda J. Martinot, Allison Boone, Gregory A. Krane, Martha E. Hensel, Shawn V. Lennix
The 2023 annual Division of Translational Toxicology (DTT) Satellite Symposium, entitled “Pathology Potpourri,” was held in Summerlin, Nevada, at the Society of Toxicologic Pathology’s 41st annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers’ talks along with select images
-
Guide for Combining Primary Tumors for Statistical Analysis in Rodent Carcinogenicity Studies Toxicol. Pathol. (IF 1.5) Pub Date : 2024-03-06 Charlotte Keenan, Muthafar Al-Haddawi, Jean-Guy Bienvenu, Alys Elizabeth Bradley, Paul Brown, Hepei Chen, Karyn Colman, Michael Elwell, Nicholas Gatto, Dawn Goodman, Binod Jacob, Lynda Lanning, LuAnn McKinney, Erin Muhlbradt, Rick Perry, Alessandro Piaia, Daniel Potenta, Karen S. Regan, Benjamin Sefing, Michael Thibodeau, Erin Tibbs-Slone, Jochen Woicke, Craig M. Zwickl
The Tumor Combination Guide was created at the request of the U. S. Food and Drug Administration (FDA) by a Working Group of biopharmaceutical experts from international societies of toxicologic pathology, the Food and Drug Administration (FDA), and members of the Standard for Exchange of Nonclinical Data (SEND) initiative, to assist pharmacology/toxicology reviewers and biostatisticians in statistical
-
Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand White Rabbit Toxicol. Pathol. (IF 1.5) Pub Date : 2024-02-22 Eric Tien, Branka Grubor, Melissa Kirkland, Su Jing Chan, Nick van der Munnik, Wenlong Xu, Kate Henry, Stefan Hamann, Cong Wei, Wan-Hung Lee, Davide Gianni, Ashton Brennecke, Kalyani Nambiar, Jeron Chen, Bin Liu, Shen Shen, Claudine Tremblay, Edward D. Plowey, Patrick Trapa, James Fikes, Junghae Suh, Dale Morris
Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted
-
Comparative Impact of Various Fasting Periods on the Welfare of Sprague-Dawley Rats With or Without Supplementation Toxicol. Pathol. (IF 1.5) Pub Date : 2024-02-21 Adeyemi O. Adedeji, Fiona Zhong, Janice Corpuz, Fangyao Hu, Xiaofeng Zhao, Dewakar Sangaraju, Catherine F. Ruff, Noel Dybdal
In nonclinical toxicology studies, lab animals are fasted typically overnight, to reduce variability in some clinical pathology parameters. However, fasting adds undue stress, and this is particularly concerning in rodents given their fast metabolic rates. Furthermore, as rodents are nocturnal animals, an overnight fasting may cause a protracted negative metabolic state even when the fasting has technically
-
Toxicologic Neuropathology of Novel Biotherapeutics Toxicol. Pathol. (IF 1.5) Pub Date : 2024-02-21 Dinesh S. Bangari, Lisa G. Lanigan, Sarah D. Cramer, Jessica L. Grieves, René Meisner, Arlin B. Rogers, Elizabeth J. Galbreath, Brad Bolon
Biotherapeutic modalities such as cell therapies, gene therapies, nucleic acids, and proteins are increasingly investigated as disease-modifying treatments for severe and life-threatening neurodegenerative disorders. Such diverse bio-derived test articles are fraught with unique and often unpredictable biological consequences, while guidance regarding nonclinical experimental design, neuropathology
-
Toxicologic Pathology Forum Opinion Piece: Use of Virtual Control Groups in Nonclinical Toxicity Studies: The Anatomic Pathology Perspective Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-31 Armelle Grevot, Julie Boisclair, Magali Guffroy, Peter Hall, Gabriele Pohlmeyer-Esch, Matt Jacobsen, Ute Bach, Anna Lena Frisk, Noel Dybdal, Xavier Palazzi
In the last decade, numerous initiatives have emerged worldwide to reduce the use of animals in drug development, including more recently the introduction of Virtual Control Groups (VCGs) concept for nonclinical toxicity studies. Although replacement of concurrent controls (CCs) by virtual controls (VCs) represents an exciting opportunity, there are associated challenges that will be discussed in this
-
Toxicogenomics Approaches to Address Toxicity and Carcinogenicity in the Liver Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-30 Arun R. Pandiri, Scott S. Auerbach, Jim L. Stevens, Eric A. G. Blomme
Toxicogenomic technologies query the genome, transcriptome, proteome, and the epigenome in a variety of toxicological conditions. Due to practical considerations related to the dynamic range of the assays, sensitivity, cost, and technological limitations, transcriptomic approaches are predominantly used in toxicogenomics. Toxicogenomics is being used to understand the mechanisms of toxicity and carcinogenicity
-
Assessment of Color Reproducibility and Mitigation of Color Variation in Whole Slide Image Scanners for Toxicologic Pathology Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-30 Mei-Lan Chu, Xing-Yue M. Ge, Jeffrey Eastham, Trung Nguyen, Reina N. Fuji, Ruth Sullivan, Daniel Ruderman
Digital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of
-
Toxicologic Pathology Forum Opinion: Rational Approaches to Expanded Neurohistopathology Evaluation for Nonclinical General Toxicity Studies and Juvenile Animal Studies Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-30 Brad Bolon
Existing nervous system sampling and processing “best practices” for nonclinical general toxicity studies (GTS) were designed to assess test articles with unknown, no known, or well-known neurotoxic potential. Similar practices are applicable to juvenile animal studies (JAS). In GTS and JAS, the recommended baseline sampling for all species includes brain (7 sections), spinal cord (cervical and lumbar
-
Select Toxicologic Pathology Case Studies of the Hepatobiliary System Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-28 Allison C. Boone, Shakirat A. Adetunji, Rebecca Kohnken, Kenji Koyama
This case study session of the hepatobiliary system was held during the 42nd Annual Society of Toxicologic Pathology Symposium in Summerlin, Nevada. The case studies highlighed potential hepatic and biliary toxicity liabilities. This article comprises several of the case studies that were presented during the session which included copper-associated hepatitis in a dog, sinusoidal obstruction syndrome
-
Historical Control Background Incidence of Spontaneous Neoplastic Lesions of Sprague-Dawley Rats in 104-Week Toxicity Studies Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-28 Amit Kumar, Marie Bockenstedt, Victoria Laast, Alok Sharma
Data collected from approximately 1800 male and 1800 female Sprague-Dawley (SD) rats used in 104-week carcinogenicity studies were archived in a historical control database at Labcorp Early Development, Inc, and the neoplastic microscopic observation data from these rats were retrospectively evaluated. Historical control data can provide useful information on the range and incidence of spontaneously
-
Risk Assessment for Hepatobiliary Toxicity Liabilities in Drug Development Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-20 Richard T. Miller
Risk assessment of hepatobiliary toxicities represents one of the greatest challenges and, more often than not, one of the most rewarding activities in which toxicologic pathologists can partake, and often times lead. This is in part because each liver toxicity picture is a bit different, informed by a broad range and diversity of relevant data, and also in part because the heavily relied upon animal
-
Early-Onset Asymptomatic Polypoid Cystitis in Two Adolescent Male Beagle Dogs Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-09 Giulia Tosi, Jennifer Rachael Barnes
This brief communication describes a rare spontaneous background lesion in the lower urinary tract of two male laboratory beagles. Proliferative lesions comprising a constellation of histological features consistent with polypoid cystitis were observed in the bladder of two adolescent dogs from a routine preclinical toxicology study. Both animals were clinically asymptomatic and had only minor alterations
-
Toxicologic Pathology Forum: Opinion on Interpretive Challenges for Procedure-Related Effects Associated With Direct Central Nervous System Delivery of Oligonucleotides to Rodents, Dogs, and Nonhuman Primates Toxicol. Pathol. (IF 1.5) Pub Date : 2024-01-05 Lisa D. Berman-Booty, Stephanie K. Klein, Curt Mazur, Joseph Schroeder, Sven Korte, Florian T. Ludwig, Annette Romeike, Brad Bolon, Jessica L. Grieves
Direct delivery of therapeutics to the central nervous system (CNS) greatly expands opportunities to treat neurological diseases but is technically challenging. This opinion outlines principal technical aspects of direct CNS delivery via intracerebroventricular (ICV) or intrathecal (IT) injection to common nonclinical test species (rodents, dogs, and nonhuman primates) and describes procedure-related
-
Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-11-20 Chitra Saran,Kim L R Brouwer
Drug-induced liver injury (DILI) remains a major concern in drug development from a patient safety perspective because it is the leading cause of acute liver failure. One mechanism of DILI is altered bile acid homeostasis and involves several hepatic bile acid transporters. Functional impairment of some hepatic bile acid transporters by drugs, disease, or genetic mutations may lead to toxic accumulation
-
Safety Findings of Dosing Gene Therapy Vectors in NHP With Pre-existing or Treatment-Emergent Anti-capsid Antibodies. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-11-03 Sundeep Chandra,Brian R Long,Carlos Fonck,Andrew C Melton,Jeremy Arens,Jill Woloszynek,Charles A O'Neill
Replication-incompetent adeno-associated virus (AAV)-based vectors are nonpathogenic viral particles used to deliver therapeutic genes to treat multiple monogenic disorders. AAVs can elicit immune responses; thus, one challenge in AAV-based gene therapy is the presence of neutralizing antibodies against vector capsids that may prevent transduction of target cells or elicit adverse findings. We present
-
Can Historical Control Group Data Be Used to Replace Concurrent Controls in Animal Studies? Toxicol. Pathol. (IF 1.5) Pub Date : 2023-10-31 Thomas Steger-Hartmann,Matthew Clark
The availability of large amounts of high-quality control data from tightly controlled regulated animal safety data has created the idea to re-use these data beyond its classical applications of quality control, identification of treatment-related effects and assessing effect-size relevance for building virtual control groups (VCGs). While the ethical and cost-saving aspects of such a concept are immediately
-
Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-10-24 Misaki Inoue,Shinya Miyazaki,Natsumi Kobayashi,Akihisa Kangawa,Tomoaki Murakami
The minipig has been used as a non-rodent species in nonclinical toxicology studies, but little is known about amyloid A (AA) amyloidosis in this species. Among domestic pigs, reports of AA amyloidosis have been limited to animals with mutations in the N-terminal residue of serum AA (SAA), which is thought to be a primary etiological factor. In this study, we histologically examined 26 microminipigs
-
An Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-09-29 Laurence O Whiteley
This article reviews the presentation given at the 2023 annual meeting of the Society of Toxicologic Pathology (STP) on liver toxicity observed with adeno-associated viral vector (AAV) gene therapy. After decades as a therapeutic modality largely confined to the academic research environment, gene therapy has emerged in recent years as a rapidly expanding therapeutic approach in the biopharmaceutical
-
Reduced Fasting Duration in Cynomolgus Monkeys Enhances Animal Welfare During Toxicology Studies. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-09-13 Adeyemi O Adedeji,Tony Pourmohamad,Niraj Tripathi,Shelly Zhong,Kenna R Degner,Fiona Zhong,Dewakar Sangaraju,Kevin Williams,Noel Dybdal
During toxicology studies, fasting animals prior to clinical pathology blood collection is believed to reduce variability in some clinical chemistry analytes. However, fasting adds stress to animals that are already stressed from the administration of potentially toxic doses of the test article. The purpose of this study was to assess the impacts of different fasting durations on cynomolgus monkeys'
-
Comparative Analysis of Hypertensive Tubulopathy in Animal Models of Hypertension and Its Relevance to Human Pathology. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-08-26 Alex A Gutsol,Taben M Hale,Jean-Francois Thibodeau,Chet E Holterman,Rania Nasrallah,Jose W N Correa,Rhian M Touyz,Chris R J Kennedy,Dylan Burger,Richard L Hébert,Kevin D Burns
Assessment of hypertensive tubulopathy for more than fifty animal models of hypertension in experimental pathology employs criteria that do not correspond to lesional descriptors for tubular lesions in clinical pathology. We provide a critical appraisal of experimental hypertension with the same approach used to estimate hypertensive renal tubulopathy in humans. Four models with different pathogenesis
-
Musings on Education for Toxicologic Pathology Proficiency in a Post-pandemic, Remotely Working World. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-08-14 Brad Bolon
-
Toxicologic Pathology Forum: Considerations Regarding Determination of Adversity for Immunopathology Findings in Nonclinical Toxicology Studies with Immune-Modulating Therapeutics. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-08-14 Tracey L Papenfuss,Lauren Himmel,C Frieke Kuper,Sunish Mohanan,Johannes Harleman,Susan A Elmore
The evaluation of changes in the immune system serves to determine the efficacy and potential immunotoxicologic effects of new products under development. Toxicologic pathologists play critical roles in identifying immune system changes that drive the immunosafety determination. Standard pathology evaluations of therapies and chemicals remain similar; however, biopharmaceutical therapies have moved
-
Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-07-25 Bindu M Bennet,Ingrid D Pardo,Basel T Assaf,Elizabeth Buza,Sarah Cramer,LaTasha K Crawford,Jeffery A Engelhardt,Branka Grubor,James P Morrison,Tanasa S Osborne,Alok K Sharma,Brad Bolon
Certain biopharmaceutical products consistently affect dorsal root ganglia, trigeminal ganglia, and/or autonomic ganglia. Product classes targeting ganglia include antineoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, and anti-nerve growth factor agents. This article outlines "points to consider" for sample collection, processing, evaluation, interpretation
-
European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-07-14 Josep M Monné Rodríguez,Anna-Lena Frisk,Robert Kreutzer,Thomas Lemarchand,Stephane Lezmi,Chandrassegar Saravanan,Birgit Stierstorfer,Céline Thuilliez,Enrico Vezzali,Grazyna Wieczorek,Seong-Wook Yun,Dirk Schaudien
In situ hybridization (ISH) is used for the localization of specific nucleic acid sequences in cells or tissues by complementary binding of a nucleotide probe to a specific target nucleic acid sequence. In the last years, the specificity and sensitivity of ISH assays were improved by innovative techniques like synthetic nucleic acids and tandem oligonucleotide probes combined with signal amplification
-
Neurofilament Light Chain: A Translational Safety Biomarker for Drug-Induced Peripheral Neurotoxicity. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-07-12 Diethilde Theil,Jens Kuhle,Dominique Brees,Elaine Tritto,François Pognan,Wilfried Frieauff,Kelley Penraat,Emily Meseck,Reginald Valdez,Andreas Hartmann
Branaplam is a splicing modulator previously under development as a therapeutic agent for Spinal Muscular Atrophy Type 1 and Huntington's disease. Branaplam increased the levels of survival motor neuron protein in preclinical studies and was well tolerated in early clinical studies; however, peripheral neurotoxicity was observed in a preclinical safety study in juvenile dogs. The aim of this study
-
Retinal and Systemic Toxicity of Vigabatrin Is Driven by the S-Enantiomer in the Long Evans Rat. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-07-04 Allan D Rasmussen,Nathalie Truchot,Agnete Dyssegaard,Pierluigi Fant
In this study, we assessed the toxicity and toxicokinetics of racemic vigabatrin and its S- and R-enantiomers (vigabatrin consists of 50:50% of the two enantiomers) by administering doses of the three test articles to male Long Evans rats via oral gavage. The animals were housed under high-intensity light conditions and the study consisted of an escalating dose phase and a 21-day fixed-dose phase.
-
Results of the European Society of Toxicologic Pathology Survey on the Use of Artificial Intelligence in Toxicologic Pathology. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-06-01 Xavier Palazzi,Erio Barale-Thomas,Bhupinder Bawa,Jonathan Carter,Kyathanahalli Janardhan,Heike Marxfeld,Abraham Nyska,Chandrassegar Saravanan,Dirk Schaudien,Vanessa L Schumacher,Robert H Spaet,Simone Tangermann,Oliver C Turner,Enrico Vezzali
The European Society of Toxicologic Pathology (ESTP) initiated a survey through its Pathology 2.0 workstream in partnership with sister professional societies in Europe and North America to generate a snapshot of artificial intelligence (AI) usage in the field of toxicologic pathology. In addition to demographic information, some general questions explored AI relative to (1) the current status of adoption
-
Absence of Increased Susceptibility to Acetaminophen-Induced Liver Injury in a Diet-Induced NAFLD Mouse Model Toxicol. Pathol. (IF 1.5) Pub Date : 2023-05-09 Takeshi Izawa, Gregory S. Travlos, Ricardo A. Cortes, Natasha P. Clayton, Robert C. Sills, Arun R. Pandiri
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease and its influence on drug-induced liver injury (DILI) is not fully understood. We investigated whether NAFLD can influence...
-
Assessing the Carcinogenicity of Vadadustat, an Oral Hypoxia-Inducible Factor Prolyl-4-Hydroxylase Inhibitor, in Rodents Toxicol. Pathol. (IF 1.5) Pub Date : 2023-05-09 Heather Kowalski, Debie Hoivik, Michael Rabinowitz
Vadadustat is an investigational oral hypoxia-inducible factor (HIF) prolyl-4-hydroxylase inhibitor to treat anemia due to chronic kidney disease (CKD). Some studies suggest that HIF activation pro...
-
Corrigendum to Histology Atlas of the Developing Mouse Placenta. Toxicol. Pathol. (IF 1.5) Pub Date : 2023-05-09
-
Toxicologic Pathology Forum: Opinion on Performing Good Laboratory Practice Histopathology Evaluation for Nonclinical Toxicity Studies in a Remote Location Toxicol. Pathol. (IF 1.5) Pub Date : 2023-04-26 Renee R. Hukkanen, Michelle Trapani, Tana Derringer, Victoria Laast, Zbigniew W. Wojcinski, Rosa Anna Manno, Matthias Rinke, Eric van Esch, Alys E. Bradley, Patrizia Cristofori, Roger Alison, Barb Munch
Toxicologic/veterinary pathologists are working remotely from Good Laboratory Practice (GLP) test facilities (TFs) in increasing numbers, most commonly in home-office settings. A study pathologist ...
-
Investigation of the Proliferative Potential of FGF21 or FGF19 in Liver-Specific FGFR4-Deficient Mice Toxicol. Pathol. (IF 1.5) Pub Date : 2023-04-26 Kerstin Wäse, Thomas Bartels, Uwe Schwahn, Mostafa Kabiri
Fibroblast growth factor 21 (FGF21) and FGF15/FGF19 belong to the same subgroup of FGFs and are believed to have therapeutic potential in the treatment of type 2 diabetes and associated metabolic d...
-
Toxicologic Pathology Forum: Tissue Evaluation in Nonclinical Toxicity Studies for Prophylactic Vaccines Toxicol. Pathol. (IF 1.5) Pub Date : 2023-04-21 Rani S. Sellers
Nonclinical toxicity testing (GLP) of prophylactic vaccines to support human clinical trials is outlined in the World Health Organization nonclinical vaccine-development guidelines, which are follo...
-
Early-Onset albuminuria and Associated Renal Pathology in Leucine-Rich Repeat Kinase 2 Knockout Rats Toxicol. Pathol. (IF 1.5) Pub Date : 2023-04-20 Yi-Zhong Gu, Katerina Vlasakova, Glen Miller, Nicholas T. Gatto, Paul J. Ciaccio, Sabu Kuruvilla, Elizabeth G. Besteman, Roger Smith, Spencer J. Reynolds, Rupesh P. Amin, Warren E. Glaab, Gordon Wollenberg, Jose Lebron, Frank D. Sistare
Activating mutations of the leucine-rich repeat kinase 2 (LRRK2) gene are associated with Parkinson disease (PD), prompting development of LRRK2 inhibitors as potential treatment for PD. However, k...
-
Toxicologic Pathology Forum Opinion: Interpretation of Gliosis in the Brain and Spinal Cord Observed During Nonclinical Safety Studies Toxicol. Pathol. (IF 1.5) Pub Date : 2023-04-14 Brad Bolon
Gliosis, defined as a nonneoplastic reaction (hypertrophy and/or proliferation) of astrocytes and/or microglial cells, is a frequent finding in the central nervous system (CNS [brain and/or spinal ...
-
Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice Toxicol. Pathol. (IF 1.5) Pub Date : 2023-04-03 Thai-Vu T. Ton, Hue-Hua L. Hong, Ramesh C. Kovi, Keith R. Shockley, Shyamal D. Peddada, Kevin E. Gerrish, Kyathanahalli S. Janardhan, Gordon Flake, Mathew D. Stout, Robert C. Sills, Arun R. Pandiri
Antimony trioxide (AT) is used as a flame retardant in fabrics and plastics. Occupational exposure in miners and smelters is mainly through inhalation and dermal contact. Chronic inhalation exposur...
-
Assessment of Mouse Liver Histopathology Following Exposure to HFPO-DA With Emphasis on Understanding Mechanisms of Hepatocellular Death Toxicol. Pathol. (IF 1.5) Pub Date : 2023-03-29 Chad M. Thompson, Melissa M. Heintz, Jeffrey C. Wolf, Roza Cheru, Laurie C. Haws, John M. Cullen
Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (HFPO-DA) is a short chain member of per- and polyfluoroalkyl substances (PFAS). To better understand the relevance of histopathologic...
-
Cardiac Rhabdomyoma in Four Göttingen Minipigs Toxicol. Pathol. (IF 1.5) Pub Date : 2023-02-01 Laine E. Feller, Aaron Sargeant, E. J. Ehrhart, Bethany Balmer, Keith Nelson, Jennifer Lamoureux
Göttingen minipigs are increasingly used as an alternative large animal model in nonclinical toxicology studies, and proliferative lesions in this species are rare. Here, we report four cases of ca...
-
Toxicologic Pathology Forum: Opinion on Approaches for Reporting Toxic and Adverse Dose Levels in Nonclinical Toxicology Studies Supporting the Development of Anticancer Pharmaceuticals Toxicol. Pathol. (IF 1.5) Pub Date : 2023-01-25 Renee R. Hukkanen, Tomoyuki Moriyama, Daniel J. Patrick, Jonathan Werner
The advancement of an investigational new drug in humans is a significant developmental milestone. In first-in-human (FIH)-enabling toxicology studies, the highest dose without a test article–relat...
-
Pharmacobezoar Formation From HPMC-AS-Containing Spray-Dried Formulations in Nonclinical Safety Studies in Rats Toxicol. Pathol. (IF 1.5) Pub Date : 2022-12-21 Hannes Gierke, Teresa Pfrommer, Kerstin Schäfer, Werner Weitschies, Thomas Nolte
Changing the physical state from crystalline to amorphous is an elegant method to increase the bioavailability of poorly soluble new chemical entity (NCE) drug candidates. Subsequently, we report f...
-
Scientific and Regulatory Policy Committee Best Practices*: Recommended (“Best”) Practices for Informed (Non-blinded) Versus Masked (Blinded) Microscopic Evaluation in Animal Toxicity Studies Toxicol. Pathol. (IF 1.5) Pub Date : 2022-11-14 Brad Bolon, Sabine Francke, Jessica M. Caverly Rae, Evelyne Polack, Karen S. Regan, Elizabeth F. McInnes, Jamie K. Young, Kevin Keane, Rick Perry, Annette Romeike, Karyn Colman, Karl Jensen, Kyoko Nakano-Ito, Elizabeth J. Galbreath
This article describes the Society of Toxicologic Pathology’s (STP) five recommended (“best”) practices for appropriate use of informed (non-blinded) versus masked (blinded) microscopic evaluation ...
-
Black Cohosh Herbal Extract and Hematologic Alterations in B6C3F1/N Mice Toxicol. Pathol. (IF 1.5) Pub Date : 2022-11-14 Michelle Cora
Black cohosh is a readily available dietary supplement currently marketed as a remedy for dysmenorrhea and menopausal symptoms and is one of the top-selling herbal supplements in the United States....
-
Toxicologic Pathology Forum*: A Roadmap for Building State-of-the-Art Digital Image Data Resources for Toxicologic Pathology in the Pharmaceutical Industry Toxicol. Pathol. (IF 1.5) Pub Date : 2022-11-05 Xing-Yue Ge, Juergen Funk, Tom Albrecht, Merima Birkhimer, Moritz Gilsdorf, Matthew Hayes, Fangyao Hu, Pierre Maliver, Mark McCreary, Trung Nguyen, Fernando Romero-Palomo, Shanon Seger, Reina N. Fuji, Vanessa Schumacher, Ruth Sullivan
Digitization of histologic slides brings with it the promise of enhanced toxicologic pathology practice through the increased application of computational methods. However, the development of these...
-
Neutropenia in Cynomolgus Monkeys With Anti-Drug Antibodies Associated With Administration of Afucosylated Humanized Monoclonal Antibodies Toxicol. Pathol. (IF 1.5) Pub Date : 2022-11-03 Adeyemi O. Adedeji, Fiona Zhong, Jennifer A. Getz, Zoe Zhong, Wendy Halpern
Removal of the core fucose from the Fc region of humanized monoclonal antibodies (afucosylated antibodies) enhances their antibody-dependent cell cytotoxicity activities in killing cancer cells. Ba...
-
Methodologies and Emerging Technologies for the Evaluation of the Hematopoietic System Toxicol. Pathol. (IF 1.5) Pub Date : 2022-10-28 Florence Poitout-Belissent, Allison Vitsky, Mark A. Smith, Madhu P. Sirivelu
Hematology and bone marrow analysis is central to our understanding of the hematopoietic system and how it responds to insults, and this session presented during the 2022 STP symposium provided a r...
-
Toxicologic Pathology Forum: Opinion on Not Euthanizing Control Animals in the Recovery Phase of Non-Rodent Toxicology Studies Toxicol. Pathol. (IF 1.5) Pub Date : 2022-10-13 Kyathanahalli S. Janardhan, Radhakrishna Sura, Smita Salian-Mehta, Thierry Flandre, Xavier Palazzi, Doris Zane, Bhanu Singh, Binod Jacob, Renee Rosemary Hukkanen, Muthafar Al-Haddawi, Bindu Bennet, Victoria Laast, Donna Lee, Richard Peterson, II, Annette Romeike, Frederic Schorsch, Magali Guffroy
Nonclinical toxicology studies that are required to support human clinical trials of new drug candidates are generally conducted in a rodent and a non-rodent species. These studies typically contai...
-
Extraintestinal Pathogenic Escherichia Coli Causes Necrohemorrhagic Pneumonia in Multiple Research Dogs Toxicol. Pathol. (IF 1.5) Pub Date : 2022-10-06 Sarah E. Coe, Michelle A. Magagna, Annie Zimmerman, April George, Caitlyn Carter, Charissa Dean, Keith Nelson
Extraintestinal pathogenic Escherichia coli expressing cytotoxic necrotizing factor (CNF) 1 and 2 virulence factors is a rarely reported cause of acute, fatal necrohemorrhagic pneumonia in canines....
-
Gemtuzumab Ozogamicin Treatment Results in Decreased Proliferation and Differentiation of Human Megakaryocytes but Does Not Inhibit Mature Platelet Function Toxicol. Pathol. (IF 1.5) Pub Date : 2022-10-06 Allison Vitsky, Aida Sacaan, Wenyue Hu, Martin Finkelstein, William Reagan
Mylotarg (Gemtuzumab ozogamicin [GO]), an antibody drug conjugate comprising a CD33-directed antibody linked to calicheamicin, is approved for use in certain acute myeloid leukemia patients. Follow...
-
Identifying Erythrocyte Injury in Toxicology Studies Toxicol. Pathol. (IF 1.5) Pub Date : 2022-10-06 Erica Behling-Kelly
The hematological impacts of a drug can affect erythropoiesis at the level of the bone marrow, or decrease the life span of the RBC (red blood cell). The most common and recognizable clinical manif...
-
Proceedings of the 2022 National Toxicology Program Satellite Symposium Toxicol. Pathol. (IF 1.5) Pub Date : 2022-09-27 Erin M. Quist, Shambhunath Choudhary, Richard Lang, Debra A. Tokarz, Mark Hoenerhoff, Jonathan Nagel, Jeffrey I. Everitt
The 2022 annual National Toxicology Program Satellite Symposium, entitled “Pathology Potpourri,” was held in Austin, Texas at the Society of Toxicologic Pathology’s 40th annual meeting during a hal...
-
Deep Learning–Based Segmentation of Morphologically Distinct Rat Hippocampal Reactive Astrocytes After Trimethyltin Exposure Toxicol. Pathol. (IF 1.5) Pub Date : 2022-09-20 Miika Vuorimaa, Ilona Kareinen, Petri Toivanen, Stefan Karlsson, Saku Ruohonen
As regulators of homeostasis, astrocytes undergo morphological changes after injury to limit the insult in central nervous system (CNS). Trimethyltin (TMT) is a known neurotoxicant that induces rea...
-
To Clot or Not to Clot: Deepening Our Understanding of Alterations in the Hemostatic System Toxicol. Pathol. (IF 1.5) Pub Date : 2022-09-17 William J. Reagan, Marjory B. Brooks, Renata Grozovsky, Debra Pittman, Allison Vitsky, Karrie Brenneman
The session on the hemostatic system focused on new developments in coagulation and platelet biology as well as how therapeutic agents may affect hemostasis. The classic cascade model of coagulatio...
-
Pathology of Bone: Changes Associated With Different Classes of Compounds Toxicol. Pathol. (IF 1.5) Pub Date : 2022-09-16 Kathryn E. Gropp
During this presentation, a variety of class effects were reviewed by their differing effects on bone, including inhibition of endochondral ossification, inhibition of the growth hormone-insulin-li...
-
How Does Lifestyle Affect Hematopoiesis and the Bone Marrow Microenvironment? Toxicol. Pathol. (IF 1.5) Pub Date : 2022-09-16 James J. Vanhie, Michael De Lisio
Lifestyle factors are modifiable behavioral factors that have a significant impact on health and longevity. Diet-induced obesity and physical activity/exercise are two prevalent lifestyle factors t...
-
Overview of Session 3 Mechanisms of Decreased Erythropoiesis and Erythroid Cell Injury Toxicol. Pathol. (IF 1.5) Pub Date : 2022-09-05 A. Eric Schultze, Lila Ramaiah
This session, held during the 41st Annual STP Symposium, focused on mechanisms of decreased erythropoiesis and erythroid cell injury. The speakers provided comprehensive overviews of physiologic an...