The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology. The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field. The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.
Daniel C. Millard, Qianyu Dang, Hong Shi, Xiaou Zhang, Chris Strock, Udo Kraushaar, Haoyu Zeng, Paul Lévesque, H. R. Lu, Jean‐Frédéric Gerbeau, Joseph C. Wu, Yingxin Li, Greg Luerman, Blake D. Anson, Liang Guo, Mike Clements, Yama Abassi, James D. Ross, Jennifer Pierson, Gary A. Gintant
Ksenia Blinova, Jayna Stohlman, José Vicente, Dulciana Chan, Lars Johannesen, María P. Hortigón-Vinagre, Víctor Zamora, Godfrey L. Smith, William Crumb, Li Pang, Beverly Lyn‐Cook, Jonathan Ross, Mathew Brock, Stacie A. Chvatal, Daniel C. Millard, Loriano Galeotti, Norman Stockbridge, David G. Strauss
Donald S. Anderson, Esther S. Patchin, Rona M. Silva, Dale Uyeminami, Arjun Sharmah, Ting Guo, Gautom Kumar Das, Jared M. Brown, Jonathan H. Shannahan, Terry Gordon, Lung‐Chi Chen, Kent E. Pinkerton, Laura S. Van Winkle
John F. Wambaugh, R. Woodrow Setzer, Ann M. Pitruzzello, Jie Liu, David M. Reif, Nicole Kleinstreuer, Nina Ching Y. Wang, Nisha S. Sipes, Matthew T. Martin, Kaberi Das, Jamie C. DeWitt, Mark J. Strynar, Richard Judson, Keith A. Houck, Christopher Lau
Mahbubul H. Riad, Ronald E. Baynes, Lisa A. Tell, Jennifer L. Davis, Fiona P. Maunsell, Jim E. Riviere, Zhoumeng Lin
AbstractOxytetracycline (OTC) is a widely used antibiotic in food-producing animals. Extralabel use of OTC is common and may lead to violative residues in edible tissues. It is important to have a quantitative tool to predict scientifically based withdrawal intervals (WDIs) after extralabel use in food animals to ensure human food safety. This study focuses on developing a physiologically based pharmacokinetic (PBPK) model for OTC in sheep and goats. The model included 7 compartments: plasma, lung, liver, kidneys, muscle, fat, and rest of the body. The model was calibrated with serum and tissue (liver, muscle, kidney, and fat) concentration data following a single intramuscular (IM, 20 mg/kg) and/or intravenous (IV, 10 mg/kg) administration of a long-acting formulation in sheep and goats. The model was evaluated with independent datasets from Food Animal Residue Avoidance Databank (FARAD). Results showed that the model adequately simulated the calibration datasets with an overall estimated coefficient of determination (R2) of 0.95 and 0.92, respectively, for sheep and goat models and had acceptable accuracy for the evaluation datasets. Monte Carlo sampling technique was applied to predict the time needed for drug concentrations in edible tissues to fall below tolerances for the 99th percentiles of the population. The model was converted to a web-based interactive PBPK (iPBPK) interface to facilitate model applications. This iPBPK model provides a useful tool to estimate WDIs for OTC after extralabel use in small ruminants to ensure food safety and serves as a basis for extrapolation to other tetracycline drugs and other food animals.
Inchio Lou, John F. Wambaugh, Christopher Lau, Robert C. Hanson, Andrew B. Lindstrom, Mark J. Strynar, Robert D. Zehr, R. Woodrow Setzer, Hugh A. Barton
Wei-Chun Chou, Lisa A. Tell, Ronald E. Baynes, Jennifer L. Davis, Fiona P. Maunsell, Jim E. Riviere, Zhoumeng Lin
AbstractViolative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.