Article
Pharmacology & Pharmacy
G. P. Gakis, A. Krikas, P. Neofytou, L. Tran, C. Charitidis
Summary: This study estimates and discusses the biodistribution of inhaled gold nanoparticles (AuNPs) in the human body through the comparison of a model with clinical data. The results show that the extrapolated model is consistent with experimental data and provides insights into the mechanisms of inhaled AuNP translocation to the blood circulation.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Toxicology
Marco Dilger, Klaus Schneider, Claudia Drossard, Heidi Ott, Eva Kaiser
Summary: This study aimed to improve the empirical database of time, interspecies, and intraspecies extrapolation when deriving occupational exposure limits (OELs). Distributions were derived for each extrapolation step to model the associated uncertainties. The study found that using NTP data produced more reliable results than using REACH data. Additionally, observed interspecies differences confirmed the suitability of allometric scaling.
JOURNAL OF APPLIED TOXICOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Christos Kaikousidis, Aristides Dokoumetzidis
Summary: This study developed a PBPK model for the radiopharmaceutical Tc99m-Tetrofosmin in humans and conducted dosimetry studies in children. The results showed that the doses in children were higher than in adults, and the maximum administered activity scaled proportionally to body weight.
PHARMACEUTICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Keyur R. Parmar, Pradeep B. Lukka, Santosh Wagh, Zaid H. Temrikar, Jiuyu Liu, Richard E. Lee, Miriam Braunstein, Anthony J. Hickey, Gregory T. Robertson, Mercedes Gonzalez-Juarrero, Andrea Edginton, Bernd Meibohm
Summary: Spectinamides 1599 and 1810 are being developed as potential treatments for multidrug-resistant and extensively drug-resistant tuberculosis. A physiologically based pharmacokinetic (PBPK) model has been developed to predict the pharmacokinetics of these compounds in various tissues, including those relevant to tuberculosis infection. The model accurately predicts the drug exposure in mice and rats, and can be used to optimize the dosing regimens.
Review
Pharmacology & Pharmacy
Marilyn N. Martinez, Jonathan P. Mochel, Sibylle Neuhoff, Devendra Pade
Summary: This review highlights the differences in drug pharmacokinetics between dogs and humans, aiding in canine-human PK extrapolations and supporting reverse PK extrapolations. By comparing physiology, drug transporter/enzyme factors, and providing additional critical points through in-depth discussions, the review aims to encourage research that enhances the understanding of similarities and differences in drug PK between humans and dogs.
Article
Pharmacology & Pharmacy
Zhongxia Tan, Youxi Zhang, Chao Wang, Le Sun
Summary: This study aimed to develop PBPK models for simulating cefadroxil concentrations in plasma and tissues in mouse, rat, and human, which were validated and demonstrated to be rational and accurate. The models suggest that hPEPT1 is the major transporter responsible for oral absorption of cefadroxil in humans and that plasma concentration-time profiles of cefadroxil are not sensitive to dissolution rates faster than 2 hours.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Environmental Sciences
Mace G. Barron, Faith N. Lambert
Summary: In this study, Interspecies correlation estimation (ICE) models were developed for soil invertebrates using a database of 853 records encompassing 192 chemicals and 12 species. Although ICE models showed high accuracy within species order, there was less prediction accuracy in the across-taxa models, indicating the potential for further refinement and development of these models for soil organisms.
Article
Pharmacology & Pharmacy
Chaozhuang Shen, Dahu Liang, Xiaohu Wang, Wenxin Shao, Kuo Geng, Xingwen Wang, Hua Sun, Haitang Xie
Summary: A physiologically based pharmacokinetic (PBPK) model of PTU was developed to predict its pharmacokinetic characteristics in different populations. The study found that dose adjustments are necessary for pediatric patients to achieve the same plasma exposure levels, while elderly patients do not require dose adjustments. This study provides important information for individualized drug administration and evaluation in the clinical setting.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Paritosh Pande, Erin P. Madeen, David E. Williams, Susan R. Crowell, Ted J. Ognibene, Ken W. Turteltaub, Richard A. Corley, Jordan N. Smith
Summary: A PBPK model was developed to study the metabolism of DBC in mice and humans, and the model was validated with experimental data. The simulations showed that interspecies differences in metabolism and physiology have significant implications for internal dose assessment.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Review
Environmental Sciences
Harvey J. Clewell, Phyllis C. Fuchsman
Summary: This article examines the differences in default extrapolation approaches used in human health risk assessments and ecological risk assessments, discusses the factors influencing inter-species variability in chemical exposures, and proposes alternative methodologies for more accurate interspecies extrapolations in wildlife ERAs.
INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT
(2023)
Review
Environmental Sciences
Sanne J. P. van den Berg, Lorraine Maltby, Tom Sinclair, Ruoyu Liang, Paul J. van den Brink
Summary: This review discusses existing cross-species extrapolation methodologies, emphasizing the benefits of modelling approaches based on ecologically relevant and robust effects for risk assessment. It also explores predictors useful for explaining differences in species sensitivity, highlighting the importance of addressing heterogeneity in training data for model reliability. Additionally, statistical considerations are examined, recommending publication of scientific code with studies to clarify modelling choices and improve understanding of the resulting models.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Chemistry, Multidisciplinary
Agnieszka Gajewicz-Skretna, Supratik Kar, Magdalena Piotrowska, Jerzy Leszczynski
Summary: The ability to accurately predict biological responses of chemicals makes QSAR/QSPR/QSTR models unique. These models need to be validated using various metrics, with error-based metrics being especially important. The KwLPR algorithm shows better predictive quality than traditional approaches, demonstrating its advantage and reliability as a novel cheminformatic tool.
JOURNAL OF CHEMINFORMATICS
(2021)
Article
Medicine, Research & Experimental
Fang-Ching Chao, Eloisa Berbel Manaia, Gilles Ponchel, Chien-Ming Hsieh
Summary: By using a physiologically-based pharmacokinetic (PBPK) model, we quantitatively assessed the cellular toxicity of the chemotherapeutic drug doxorubicin, and found that clinical dosing regimens can mitigate the risk of adverse effects.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Environmental Sciences
Kyle W. Blackburn, Zamir Libohova, Kabindra Adhikari, Charles Kome, Xander Maness, Miles R. Silman
Summary: Soil organic carbon plays a critical role in major ecosystem processes, agriculture, and climate mitigation. This study examined the distribution of SOC stock based on land use and topography and assessed the scalability of SOC stock predictions. The results showed that land use, topography, and soil depth were related to SOC stock distribution, and accuracy predictions were influenced by data source.
Article
Toxicology
Jerry L. Campbell, Harvey J. Clewell III, Cynthia Van Landingham, P. Robinan Gentry, Athena M. Keene, Michael D. Taylor, Melvin E. Andersen
Summary: An updated PBPK model for manganese has been developed and successfully described the kinetics of manganese in tissues in both monkeys and humans. This model eliminates the need for relying solely on cadaver data and whole-body tracer studies to calibrate a human model, increasing the biological relevance and confidence in using the manganese PBPK models for risk assessment.
TOXICOLOGICAL SCIENCES
(2023)
Article
Environmental Sciences
Lesa L. Aylward, Sean M. Hays, Angelika Zidek
JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
(2017)
Article
Environmental Sciences
Yiqin Chen, Andreas Sjodin, Michael S. McLachlan, Karin English, Lesa L. Aylward, Leisa-Maree L. Toms, Julie Varghese, Peter D. Sly, Jochen F. Mueller
ENVIRONMENT INTERNATIONAL
(2017)
Article
Public, Environmental & Occupational Health
A. L. Heffernan, T. K. Cunningham, D. S. Drage, L. L. Aylward, K. Thompson, S. Vijayasarathy, J. F. Mueller, S. L. Atkin, T. Sathyapalan
INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH
(2018)
Article
Medicine, Legal
Sean M. Hays, Devika Poddalgoda, Kristin Macey, Lesa Aylward, Andy Nong
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2018)
Article
Medicine, Legal
Lesa L. Aylward, Kim Irwin, Annie St-Amand, Andy Nong, Sean M. Hays
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2018)
Article
Environmental Sciences
Leisa-Maree L. Toms, Andreas Sjodin, Peter Hobson, Fiona A. Harden, Lesa L. Aylward, Jochen F. Mueller
ENVIRONMENT INTERNATIONAL
(2018)
Article
Environmental Sciences
Peter Fantke, Lesa Aylward, Jane Bare, Weihsueh A. Chiu, Robin Dodson, Robert Dwyer, Alexi Ernstoff, Brett Howard, Matti Jantunen, Olivier Jolliet, Richard Judson, Nienke Kirchhubel, Dingsheng Li, Aubrey Miller, Greg Paoli, Paul Price, Lorenz Rhomberg, Beverly Shen, Hyeong-Moo Shin, Justin Teeguarden, Daniel Vallero, John Wambaugh, Barbara A. Wetmore, Rosemary Zaleski, Thomas E. McKone
ENVIRONMENTAL HEALTH PERSPECTIVES
(2018)
Article
Environmental Sciences
Lesa Aylward, Giulia Vilone, Christina Cowan-Ellsberry, Jon A. Arnot, John N. Westgate, Cian O'Mahony, Sean M. Hays
JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
(2020)
Article
Medicine, General & Internal
David I. McBride, James J. Collins, Thomas John Bender, Kenneth M. Bodner, Lesa L. Aylward
Article
Public, Environmental & Occupational Health
L. M. L. Toms, J. Braunig, S. Vijayasarathy, S. Phillips, P. Hobson, L. L. Aylward, M. D. Kirk, J. F. Mueller
INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH
(2019)
Article
Environmental Sciences
Yan Li, Xianyu Wang, Leisa-Maree L. Toms, Chang He, Peter Hobson, Peter D. Sly, Lesa L. Aylward, Jochen F. Mueller
ENVIRONMENTAL RESEARCH
(2019)
Article
Public, Environmental & Occupational Health
Sarah Faure, Nolwenn Noisel, Kate Werry, Subramanian Karthikeyan, Lesa L. Aylward, Annie St-Amand
INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH
(2020)
Article
Environmental Sciences
Daniel S. Drage, Amy L. Heffernan, Thomas K. Cunningham, Lesa L. Aylward, Jochen F. Mueller, Thozhukat Sathyapalan, Stephen L. Atkin
ENVIRONMENTAL RESEARCH
(2019)
Article
Endocrinology & Metabolism
Harshal Deshmukh, Lesa L. Aylward, Martin Rose, Alwyn Fernandes, Peter Sedman, Natalie J. Thatcher, Stephen L. Atkin, Thozhukat Sathyapalan
CLINICAL ENDOCRINOLOGY
(2020)
Article
Environmental Sciences
Marc-Andre Verner, Hassan Salame, Conrad Housand, Linda S. Birnbaum, Maryse F. Bouchard, Jonathan Chevrier, Lesa L. Aylward, Daniel Q. Naiman, Judy S. LaKind
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2020)
Article
Medicine, Legal
Fiona Sewell, Ian Ragan, Graham Horgan, David Andrew, Thomas Holmes, Irene Manou, Boris P. Mueller, Tim Rowan, Barbara G. Schmitt, Marco Corvaro
Summary: There are currently three test guidelines for acute oral toxicity studies, but the subjectivity of one guideline may be hindering its wider use. In order to address this, the NC3Rs and EPAA collaborated to analyze historical data and provide recommendations on the recognition of 'evident toxicity'.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2024)
Article
Medicine, Legal
Michael DeVito, Bas Bokkers, Majorie B. M. van Duursen, Karin van Ede, Mark Feeley, Elsa Antunes Fernandes Gaspar, Laurie Haws, Sean Kennedy, Richard E. Peterson, Ron Hoogenboom, Keiko Nohara, Kim Petersen, Cynthia Rider, Martin Rose, Stephen Safe, Dieter Schrenk, Matthew W. Wheeler, Daniele S. Wikoff, Bin Zhao, Martin van den Berg
Summary: In October 2022, the World Health Organization reevaluated the toxic equivalency factors (TEFs) for chlorinated dioxin-like compounds in a panel convened in Lisbon. This effort utilized an updated database, Bayesian dose response modeling, and meta-analysis to derive Best-Estimate TEFs. Applying these new TEFs may result in lower total toxic equivalents for dioxin-like chemicals.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2024)