Article
Pharmacology & Pharmacy
Elaina M. Kenyon
Summary: Arsenic poses challenges in PBTK model development and risk analysis, with complex metabolism and sparse information on specific metabolites. PBTK models have been used for exposure and dose-response analysis for arsenic, particularly for multi-route exposures and multiple toxic effects. Refinements to arsenic PBTK models, such as improving methylation biotransformation parameters and estimating interindividual variability, can enhance confidence in risk assessments.
Article
Engineering, Environmental
Wencai Dai, Stine Slotsbo, Cornelis A. M. van Gestel, Martin Holmstrup
Summary: Higher temperatures led to increased uptake, elimination, and bioaccumulation of organic pollutants in Enchytraeus albidus, with particularly noticeable effects under daily fluctuating temperature conditions.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Article
Environmental Sciences
Antonio Cascajosa-Lira, Concepcion Medrano-Padial, Silvia Pichardo, Jose Manuel de la Torre, Alberto Banos, Angeles Jos, Ana M. Camean
Summary: This study focused on analyzing the toxicokinetic profile of propyl-propane-thiosulfonate (PTSO) in the agricultural food sector. In silico and in vitro techniques were used to perform a pilot-study, and ecotoxicity studies were conducted to evaluate the environmental impact of the compound. The results showed the formation of detoxified metabolites and highlighted the need for further in vivo assays to confirm the findings.
ENVIRONMENTAL RESEARCH
(2023)
Article
Toxicology
Byron Kuo, Marc A. Beal, John W. Wills, Paul A. White, Francesco Marchetti, Andy Nong, Tara S. Barton-Maclaren, Keith Houck, Carole L. Yauk
Summary: Risk assessments are increasingly relying on in vitro assays for genotoxicity testing. This study evaluated 292 chemical datasets using the in vitro micronucleus test (MNvit) for hazard identification. The results identified 157 clastogenic chemicals, 25 negatives, and 110 inconclusive substances. In vitro to in vivo extrapolation (IVIVE) was used to convert concentrations into administered equivalent doses (AEDs), which were generally lower than points of departure (PODs) based on in vivo endpoints. Exposure estimates were utilized to calculate bioactivity exposure ratio (BER) values, identifying chemicals that may require additional testing.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Environmental Sciences
Anna Kreutz, Matthew S. S. Clifton, W. Matthew Henderson, Marci G. G. Smeltz, Matthew Phillips, John F. F. Wambaugh, Barbara A. A. Wetmore
Summary: Concerns about PFAS have risen due to increased knowledge about their presence, persistence, and potential to accumulate in the environment. This study evaluated the toxicokinetic properties of 73 PFAS, providing critical information about their binding, clearance, and potential transformation products. The results highlight the high binding capacity of these PFAS in plasma and their ability to undergo metabolism and abiotic loss. Understanding these factors is important for assessing the environmental fate of PFAS.
Article
Environmental Sciences
Chi-Yun Chen, Tien-Hsuan Lu, Chung-Min Liao
Summary: Marine microplastics pose a serious threat to shallow-water corals, necessitating interdisciplinary research. The ecotoxicological effects of MPs on corals are complex and need to be evaluated in a species-specific manner. Toxicokinetic and toxicodynamic modeling can help quantify the impacts of MPs on coral health and growth.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Environmental Sciences
Ferhat Ozen, Gokhan Eraslan
Summary: This study investigated the toxicokinetics of cyphenothrin in rabbits and found that while the bioavailability of oral cyphenothrin was limited, it had a long half-life and mean residence time in the body, suggesting a potential poisoning risk.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Medicine, Legal
Terry Claire, Hays Sean
Summary: The database of practical examples in toxicokinetics is growing, highlighting the importance of including TK measurements in animal studies and the future use of non-animal methods in human health risk assessments.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2022)
Review
Nanoscience & Nanotechnology
Qiran Chen, Jim E. Riviere, Zhoumeng Lin
Summary: The rapid growth of nanomaterial applications has led to concerns about human health and safety. Current research methods cannot meet the demand for efficient assessment of newly synthesized nanomaterials. This article reviews the methods for studying toxicokinetics, hazard identification, dose-response, exposure, and risk assessment of nanomaterials, identifies knowledge gaps and challenges, and discusses the potential of physiologically based pharmacokinetic models for extrapolating findings. Recent advancements in the field and future research needs are highlighted.
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
(2022)
Review
Plant Sciences
Dieter Schrenk, Joerg Fahrer, Ashley Allemang, Peter Fu, Ge Lin, Catherine Mahony, Patrick P. J. Mulder, Ad Peijnenburg, Stefan Pfuhler, Ivonne M. C. M. Rietjens, Benjamin Sachse, Barbara Steinhoff, Anja These, John Troutman, Jacqueline Wiesner
Summary: Pyrrolizidine alkaloids pose a serious threat to human health, and it is necessary to strengthen research on their toxicity and risk assessment. This paper reports on the major contributions and results of the 2nd International Workshop of Pyrrolizidine Alkaloids held in Germany in 2020, aiming to increase understanding of pyrrolizidine alkaloids and discuss risk-limiting measures in food, feed, and medicinal products.
Article
Environmental Sciences
Raymond Nepstad, Konstantinos Kotzakoulakis, Tor Nordam, JoLynn Carroll
Summary: We propose a novel approach for assessing environmental risks of discharges of produced water, taking into account explicit impact and probability. Our approach combines transport, fate, and toxicokinetic-toxicodynamic models within a super-individual framework, with a probabilistic element obtained from ensemble simulations. By considering location and species specificity, our approach addresses the dynamic nature of exposure and uptake of produced water components in the sea. Using a case study of early life stages of spawning haddock in the Barents Sea, we demonstrate the feasibility of conducting model-based risk assessments that capture the effects of natural variations in environmental conditions. We also discuss the benefits, limitations, and potential for further improvements of our approach.
MARINE POLLUTION BULLETIN
(2023)
Article
Management
Alex S. L. Tse, Harry Zheng
Summary: This paper examines a continuous-time portfolio selection problem faced by an agent with S-shaped preference, aiming to maximize utilities derived from the portfolio's periodic performance over an infinite horizon. The periodic reward structure leads to subtle incentive distortion, inducing local risk aversion in some cases, and causing underinvestment in the good states to manipulate subsequent performance evaluations in other cases. The authors outline several important elements of incentive design to mitigate long-term portfolio risk.
OPERATIONS RESEARCH
(2023)
Article
Toxicology
Christoph Hethey, Niklas Hartung, Gaby Wangorsch, Karin Weisser, Wilhelm Huisinga
Summary: A sufficient quantitative understanding of aluminium toxicokinetics in humans is lacking, but progress has been made through the development of a physiologically-based model using Al-26 tracer and a curated dataset. These advancements allow for valid predictions of aluminium levels in different tissues, paving the way for more quantitative risk assessment in humans.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Construction & Building Technology
Leela Kempton, Georgios Kokogiannakis, Paul Cooper
Summary: The study investigated 233 residential properties with previously remediated mould issues, revealing that 40% experienced regrowth within 12 months. Among the 30 properties where root cause and success of remediation were explored, it was found that remediation without addressing the root cause effectively could not prevent mould growth in the short term. Furthermore, monitoring indoor environment conditions of five properties over a year showed that high wall surface temperatures and elevated humidity levels were contributing factors to mould growth.
BUILDING AND ENVIRONMENT
(2021)
Article
Medicine, Legal
Yu-Mei Tan, Hugh A. Barton, Alan Boobis, Rachel Brunner, Harvey Clewell, Rhian Cope, Jeffrey Dawson, Jeanne Domoradzki, Peter Egeghy, Pankaj Gulati, Brandall Ingle, Nicole Kleinstreuer, Kelly Lowe, Anna Lowit, Elizabeth Mendez, David Miller, Jeffrey Minucci, James Nguyen, Alicia Paini, Monique Perron, Katherine Phillips, Hua Qian, Tharacad Ramanarayanan, Fiona Sewell, Philip Villanueva, John Wambaugh, Michelle Embry
Summary: In repeated dose animal studies, there are various methods for dose selection, including identification of apical endpoints, use of the limit dose, and determination of a maximum tolerated dose. An alternative approach, the kinetically derived maximum dose, integrates toxicokinetic data into the dose selection process as a mechanism.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2021)
Article
Toxicology
Ans Punt, Aafke Aartse, Toine F. H. Bovee, Arjen Gerssen, Stefan P. J. van Leeuwen, Ron L. A. P. Hoogenboom, Ad A. C. M. Peijnenburg
ARCHIVES OF TOXICOLOGY
(2019)
Article
Toxicology
Ans Punt, James Firman, Alan Boobis, Mark Cronin, John Paul Gosling, Martin F. Wilks, Paul A. Hepburn, Anette Thiel, Karma C. Fussell
TOXICOLOGICAL SCIENCES
(2020)
Article
Toxicology
Jochem Louisse, Martin Alewijn, Ad A. C. M. Peijnenburg, Nicole H. P. Cnubben, Minne B. Heringa, Sandra Coecke, Ans Punt
TOXICOLOGY IN VITRO
(2020)
Article
Toxicology
Rozaini Abdullah, Sebastiaan Wesseling, Bert Spenkelink, Jochem Louisse, Ans Punt, Ivonne M. C. M. Rietjens
JOURNAL OF APPLIED TOXICOLOGY
(2020)
Article
Chemistry, Medicinal
James W. Firman, Ans Punt, Mark T. D. Cronin, Alan R. Boobis, Martin F. Wilks, Paul A. Hepburn, Anette Thiel, Karma C. Fussell
Summary: The study aimed to determine the utility of high-throughput screening (HTS) data in toxicological read-across for food-relevant chemicals. Results showed that HTS data could help elucidate bioactivities, close data gaps, and define the boundaries of chemical space. The evaluation of paraben-gallates and pyranone-type compounds for estrogenicity demonstrated the potential for identifying out-of-domain compounds.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Article
Chemistry, Medicinal
Ans Punt, Nicole Pinckaers, Ad Peijnenburg, Jochem Louisse
Summary: The study developed an online PBK model toolbox for predicting chemical concentrations in vivo and prioritizing chemicals based on comparing oral equivalent doses.
CHEMICAL RESEARCH IN TOXICOLOGY
(2021)
Article
Toxicology
Ans Punt, Jochem Louisse, Nicole Pinckaers, Eric Fabian, Bennard van Ravenzwaay
Summary: The present study assesses the predictive performance of a minimal generic rat physiologically based kinetic (PBK) model to predict peak plasma concentrations (C-max) upon single oral dosing based on in vitro and in silico input data. The best performance is obtained by parameterizing the hepatic clearance, calculating partition coefficients, and using in silico calculated fraction unbound plasma and P-app values. The study provides relevant insights into the predictive performance of the model.
TOXICOLOGICAL SCIENCES
(2022)
Article
Toxicology
Ans Punt, Leonie Lautz, Geert Stoopen, Nicole Pinckaers, Deborah Rijkers, Martien Essers, Ron Hoogenboom
Summary: In vitro models using slaughterhouse-derived bovine liver S9 and precision cut liver slices successfully captured the biotransformation reactions of lidocaine in cows, confirming 2,6-dimethylaniline (DMA) as an important metabolite of lidocaine in cows. However, unlike in vivo conditions, no in vitro conversion of DMA to 4-OH-DMA was observed. Further research is needed to understand this discrepancy and to evaluate the use of slaughterhouse-derived tissue materials for predicting xenobiotics biotransformation in farm animals.
TOXICOLOGY IN VITRO
(2021)
Article
Medicine, Research & Experimental
Ans Punt, Jochem Louisse, Karsten Beekmann, Nicole Pinckaers, Eric Fabian, Bennard van Ravenzwaay, Paul L. Carmichael, Ian Sorrell, Thomas E. Moxon
Summary: The study assessed the predictive performance of a generic human PBK model based on in vitro and in silico input data, demonstrating that using specific methods in the parameterization process can improve prediction accuracy.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)
Article
Food Science & Technology
L. S. Lautz, G. Stoopen, A. J. Ginting, R. L. A. P. Hoogenboom, A. Punt Wageningen
Summary: In this study, the metabolism and elimination of fipronil in eggs were investigated using in vitro experiments and a physiologically based kinetic model. The model predictions showed good agreement with available in vivo data, indicating the potential use of the in vitro model in early phase of contamination incidents to predict the time-concentration curves.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Toxicology
Abdulkarim Najjar, Ans Punt, John Wambaugh, Alicia Paini, Corie Ellison, Styliani Fragki, Enrica Bianchi, Fagen Zhang, Joost Westerhout, Dennis Mueller, Hequn Li, Quan Shi, Timothy W. Gant, Phil Botham, Remi Bars, Aldert Piersma, Ben van Ravenzwaay, Nynke I. Kramer
Summary: With the increasing need for new methodologies and the phasing out of animal testing, interpreting in vitro assay results for quantitative hazard characterization is becoming more important. Physiologically based kinetic (PBK) models play a crucial role in extrapolating in vitro concentrations to in vivo exposures. Standardizing PBK modeling approaches is necessary for regulatory risk assessment and several steps are recommended for improvement, including defining context and implementation, harmonizing physiological input parameters, applying Good Modeling Practices (GMP), and evaluating model predictions using alternatives to in vivo data.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Toxicology
Jochem Louisse, Luca Dellafiora, Jeroen J. M. W. van den Heuvel, Deborah Rijkers, Liz Leenders, Jean-Lou C. M. Dorne, Ans Punt, Frans G. M. Russel, Jan B. Koenderink
Summary: The study assessed the transport of 7 PFASs in OAT4-transfected human embryonic kidney cells and found that all PFASs, except PFBS, were taken up by these cells. Molecular dynamics simulations supported these findings. Understanding the transport mediated by OAT4 is important for predicting the accumulation of PFASs in the human body.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Food Science & Technology
Lorenzo Pedroni, Jochem Louisse, Ans Punt, Jean Lou C. M. Dorne, Chiara Dall'Asta, Luca Dellafiora
Summary: Safrole, a natural compound, is classified as a possible human carcinogen and has been proven to be genotoxic and carcinogenic to rodents. Despite being banned in many countries, it is still widely present in spices, herbs, and essential oils. In-silico studies using molecular modeling, docking, and molecular dynamics have revealed species-specific differences in the bioactivation of safrole and provided a knowledge-based foundation for further experiments to deepen our understanding of its toxicity.
Article
Medicine, Research & Experimental
Ans Punt, Peter Bos, Betty Hakkert, Jochem Louisse
Summary: In vitro toxicokinetic data are crucial for improving chemical safety evaluations and understanding internal human chemical exposure and toxicity. This study examined the experimental variation in important parameters, such as CLint, fup, and Papp, reported in the literature. The results showed that the predicted variation in Cmax ranged from 1.4 to 28-fold and in AUC0-24h ranged from 1.4 to 23-fold due to the experimental variation in these parameters. These findings highlight the need for robust data in regulatory applications.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2023)
Article
Medicine, Research & Experimental
Ans Punt, Hans Bouwmeester, Bas J. Blaauboer, Sandra Coecke, Betty Hakkert, Delilah F. G. Hendriks, Paul Jennings, Nynke Kramer, Sibylle Neuhoff, Rosalinde Masereeuw, Alicia Paini, Ad A. C. M. Peijnenburg, Martijn Rooseboom, Michael L. Shuler, Ian Sorrell, Bart Spee, Marije Strikwold, Andries D. Van der Meer, Meike Van der Zande, Mathieu Vinken, Huan Yang, Peter M. J. Bos, Minne B. Heringa
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2020)
