Article
Agriculture, Multidisciplinary
Chen Liu, Jolijn van Mil, Annelies Noorlander, Ivonne M. C. M. Rietjens
Summary: This study developed a PBK model for EGCG and its colonic metabolites and predicted the time-dependent blood concentrations of EGCG in different feeding conditions. The results suggest that gut microbial metabolites may contribute to the activation of Nrf2 gene expression.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Toxicology
Annelies Noorlander, Mengying Zhang, Bennard van Ravenzwaay, Ivonne M. C. M. Rietjens
Summary: In this study, the ability of a new in vitro/in silico quantitative in vitro-in vivo extrapolation (QIVIVE) methodology was assessed to predict the in vivo neurotoxicity of tetrodotoxin (TTX) in rodents. The results revealed that PBK modeling-based reserve dosimetry of in vitro TTX effect data can adequately predict the in vivo neurotoxicity of TTX in rodents, providing a novel proof-of-principle for this methodology.
TOXICOLOGICAL SCIENCES
(2022)
Article
Toxicology
Isaac Omwenga, Shensheng Zhao, Laetitia Kanja, Hans Mol, Ivonne M. C. M. Rietjens, Jochem Louisse
Summary: This study developed a combined in vitro-in silico approach to predict AChE inhibition by the OP profenofos in rats and humans. The results indicate that humans are more sensitive than rats to the inhibitory effects of profenofos, mainly due to differences in kinetics. The novel approach successfully predicted in vivo AChE inhibition upon acute exposure to profenofos in rats, demonstrating its potential in chemical hazard assessment.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Environmental Sciences
Paul Quindroit, Amelie Crepet, Celine Brochot
Summary: Human biomonitoring data provide evidence of exposure to environmental chemicals, and PBPK modelling can help estimate exposure levels. In a study in France, exposure to pyrethroids was estimated based on urinary concentrations of specific metabolites. The study found no significant risks associated with the exposure levels of pyrethroids in the French cohort.
ENVIRONMENTAL RESEARCH
(2021)
Article
Toxicology
Shensheng Zhao, Sebastiaan Wesseling, Bert Spenkelink, Ivonne M. C. M. Rietjens
Summary: The study utilized PBK modeling to predict RBC AChE inhibition upon DZN exposure in humans and rats, finding that humans are 6-fold more sensitive to AChE inhibition compared to rats. By incorporating a TEF-coded PBK model with QIVIVE, an alternative testing strategy for risk assessment is provided. The predicted dose-response curves for rats matched available in vivo data on AChE inhibition, demonstrating the effectiveness of the model.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Zhoumeng Lin, Santosh Aryal, Yi-Hsien Cheng, Andre J. Gesquiere
Summary: This review article critically evaluates existing studies on in vivo pharmacokinetic properties, in vitro cellular uptake and release kinetics, and whole-body physiologically based pharmacokinetic (PBPK) modeling studies of different nanomaterials (NMs). It discusses methods for simulating in vitro and in vivo dosimetry of NMs and shares perspectives on current challenges and future directions. The article proposes a Nano-IVIVE-PBPK framework for high-throughput screening of target dosimetry and potential toxicity of NMs.
Article
Engineering, Environmental
Jiaqi Chen, Annelies Noorlander, Sebastiaan Wesseling, Hans Bouwmeester, Nynke I. Kramer, Ivonne M. C. M. Rietjens
Summary: Current climate trends will lead to a global phenomenon of intoxications caused by toxigenic microalgae and phycotoxins. Saxitoxin (STX) is a neurotoxin that can cause severe neurological symptoms in mammals when contaminated seafood is consumed. A physiologically based kinetic (PBK) modeling-facilitated quantitative in vitro to in vivo extrapolation (QIVIVE) approach was used to assess the acute neurotoxicity of oral STX exposure in humans. The integration of PBK modeling-facilitated QIVIVE and in vitro toxicity data provides a promising alternative to animal testing for human health risk assessment of phycotoxins.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jordi Minnema, Rob J. Vandebriel, Karin Boer, Walther Klerx, Wim H. De Jong, Christiaan J. E. Delmaar
Summary: Physiologically-based kinetic (PBK) modeling is a valuable tool to understand the kinetics of nanoparticles (NPs) in vivo. This study estimated PBK parameters for gold NPs (AuNPs) and compared them with other NP parameters. The results show that a small initial database is sufficient to formulate new hypotheses on NP characteristics predictive of PBK parameter values.
Article
Engineering, Environmental
Jiaqi Chen, Shensheng Zhao, Sebastiaan Wesseling, Nynke I. Kramer, Ivonne M. C. M. Rietjens, Hans Bouwmeester
Summary: This study employed PBK modeling and QIVIVE approach to investigate the neurotoxicity of organophosphate pesticides. The results showed species-specific differences in toxic response to organophosphate pesticide exposure, with humans being more susceptible. The described approach accurately predicted toxicokinetics and acute toxicity, providing evidence for its application in chemical risk assessment.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Min-Chang Kim, Young-Joo Lee
Summary: This study investigated the time-dependent pharmacokinetics of SCR430 using an ex vivo study combined with in vitro-in vivo extrapolation and physiologically based pharmacokinetic modeling. The results showed that repeated administration of SCR430 decreased systemic exposure, which was explained by increased hepatic clearance and uptake.
Article
Pharmacology & Pharmacy
Engi Abdelhady Algharably, Emma Di Consiglio, Emanuela Testai, Francesca Pistollato, Anna Bal-Price, Abdulkarim Najjar, Reinhold Kreutz, Ursula Gundert-Remy
Summary: This study used quantitative in vitro-in vivo extrapolation (QIVIVE) and Benchmark dose (BMD) modeling to predict the fetal brain effect concentration caused by oral maternal exposure to chlorpyrifos (CPF) during pregnancy. By comparing the results with epidemiological data, the contribution of in vitro endpoints to the mode of action for CPF-induced developmental neurotoxicity (DNT) was evaluated.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Nicola Melillo, Daniel Scotcher, J. Gerry Kenna, Claudia Green, Catherine D. G. Hines, Iina Laitinen, Paul D. Hockings, Kayode Ogungbenro, Ebony R. Gunwhy, Steven Sourbron, John C. Waterton, Gunnar Schuetz, Aleksandra Galetin
Summary: This study used a physiologically-based pharmacokinetic (PBPK) modeling to predict changes in the metabolism of Gadoxetate caused by different drugs. The results showed that Ciclosporin and Rifampicin significantly decreased the concentration of Gadoxetate in the liver. The effects of other drugs were marginal.
Review
Pharmacology & Pharmacy
Samarth Thakore, Arvind Sirvi, Vikram C. Joshi, Sanjali S. Panigrahi, Arijita Manna, Ridhima Singh, Abhay Sangamwar, Arvind K. Bansal
Summary: This paper critically evaluates the current state of knowledge and provides future directions for PBAM of SDDS. It outlines various methods used to retrieve physiologically relevant values for input parameters like solubility, dissolution, precipitation, lipid-digestion and permeability of SDDS. Challenges in the development of biopredictive dissolution methods due to concurrent dissolution, supersaturation, precipitation, and possible redissolution of precipitates during gastrointestinal transit of SDDS are also discussed.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Biology
Prashant Kumar, Darshan Mehta, John J. Bissler
Summary: Extracellular vesicles (EVs) are cell-derived structures that play an important role in intercellular communication and drug delivery. Physiologically based pharmacokinetic (PBPK) modeling can predict the behavior of EVs in the body and optimize drug delivery system design.
Article
Pharmacology & Pharmacy
George Loizou, Kevin McNally, Jean-Lou C. M. Dorne, Alex Hogg
Summary: The study developed a computational workflow integrating various methods to facilitate quantitative in vitro to in vivo extrapolation, and tested its accuracy using human PBK model and in vitro concentration-response data.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Toxicology
Aafke W. F. Janssen, Loes P. M. Duivenvoorde, Deborah Rijkers, Rosalie Nijssen, Ad A. C. M. Peijnenburg, Meike van der Zande, Jochem Louisse
Summary: The study evaluated the expression of CYP enzymes and chemical-induced changes in a hiPSC-derived HIO model, showing higher gene expression levels of important intestinal CYP enzymes in HIOs compared to other models. CYP3A4 activity was induced by phenobarbital and rifampicin in HIOs, indicating the potential of hiPSC-based HIOs as a useful in vitro intestinal model for studying the biotransformation of chemicals in the intestine.
ARCHIVES OF 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
Chemistry, Applied
Isaac Omwenga, Laetitia Kanja, Paul Zomer, Jochem Louisse, Ivonne M. C. M. Rietjens, Hans Mol
Summary: The study found residues of various organophosphates and carbamates pesticides in vegetables in Kenya, with some samples exceeding the EU maximum residue limits. Chlorpyrifos in spinach may pose potential health risks for children and adults in terms of acute dietary exposure. However, the risks of chronic dietary exposure are low.
FOOD ADDITIVES & CONTAMINANTS PART B-SURVEILLANCE
(2021)
Article
Food Science & Technology
Chen Liu, Jacques Vervoort, Joris van den Elzen, Karsten Beekmann, Marta Baccaro, Laura de Haan, Ivonne M. C. M. Rietjens
Summary: An in vitro fecal incubation model combined with reporter gene assay was developed to characterize interindividual differences in the gut microbial conversion of EGCG. Results showed that gallic acid and pyrogallol play a significant role in the beneficial effects of EGCG, with substantial interindividual differences in metabolite formation potentially impacting the benefits of EGCG consumption.
MOLECULAR NUTRITION & FOOD RESEARCH
(2021)
Review
Food Science & Technology
Jing Jin, Karsten Beekmann, Einar Ringo, Ivonne M. C. M. Rietjens, Fuguo Xing
Summary: The contamination of food and feed by mycotoxins is a serious global food safety problem, with fungal metabolites posing various health risks. This review explores the bi-directional interaction between major food-borne mycotoxins and the gut microbiota, as well as the potential impact of probiotics on animals exposed to mycotoxins. The role of the gut microbiota in assessing the risk of mycotoxins is crucial to fully understand their effects on health.
Article
Food Science & Technology
Jing Jin, Albertus Spenkelink, Karsten Beekmann, Marta Baccaro, Fuguo Xing, Ivonne M. C. M. Rietjens
Summary: The study reveals interspecies differences in the deacetylation of acetylated DONs, but assuming complete intestinal deconjugation is an adequate approach for risk assessment.
MOLECULAR NUTRITION & FOOD RESEARCH
(2021)
Article
Toxicology
Katja C. W. van Dongen, Meike van der Zande, Ben Bruyneel, Jacques J. M. Vervoort, Ivonne M. C. M. Rietjens, Clara Belzer, Karsten Beekmann
Summary: Fructoselysine is a potential hazard to human microbes formed during food processing, but information on the biochemical reactions and interindividual differences is limited. This study found significant interindividual variations in gut microbial degradation of fructoselysine, with Ruminococcus_1 showing a strong correlation with fructoselysine degradation and butyrate production.
TOXICOLOGY IN VITRO
(2021)
Article
Multidisciplinary Sciences
Vera Silva, Abdallah Alaoui, Vivi Schlunssen, Anne Vested, Martien Graumans, Maurice van Dael, Marco Trevisan, Nicoleta Suciu, Hans Mol, Karsten Beekmann, Daniel Figueiredo, Paula Harkes, Jakub Hofman, Ellen Kandeler, Nelson Abrantes, Isabel Campos, Maria Angeles Martinez, Joana Luisa Pereira, Dirk Goossens, Juergen Gandrass, Freya Debler, Esperanza Huerta Lwanga, Marlot Jonker, Frank van Langevelde, Martin T. Sorensen, Jerry M. Wells, Jos Boekhorst, Anke Huss, Daniele Mandrioli, Daria Sgargi, Paul Nathanail, Judith Nathanail, Lucius Tamm, Peter Fantke, Jennifer Mark, Christian Grovermann, Ana Frelih-Larsen, Irina Herb, Charlotte-Anne Chivers, Jane Mills, Francisco Alcon, Josefina Contreras, Isabelle Baldi, Igor Paskovic, Glavan Matjaz, Trine Norgaard, Virginia Aparicio, Coen J. Ritsema, Violette Geissen, Paul T. J. Scheepers
Summary: The study aims to investigate PPP residues in different farm systems and assess their impact on the environment, flora, fauna, and human health. Environmental and biological samples are being collected at various sites across Europe to analyze the impact of PPP mixtures and estimate exposures through modeling. The study will provide valuable insights to inform sustainable plant protection practices and land use policy decisions.
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
Toxicology
Jochem Louisse, Patrick P. J. Mulder, Arjen Gerssen, Geert Stoopen, Deborah Rijkers, Milou G. M. van de Schans, Ad A. C. M. Peijnenburg
Summary: “The study utilized a bioassay-directed analysis approach to identify potentially toxic PAs not yet included in monitoring programs. The findings suggest that this method is effective in identifying candidate PAs with genotoxic activity.”
ARCHIVES OF TOXICOLOGY
(2022)
Article
Food Science & Technology
Katja C. W. van Dongen, Leonie Kappetein, Ignacio Miro Estruch, Clara Belzer, Karsten Beekmann, Ivonne M. C. M. Rietjens
Summary: This review investigates the roles of endogenously versus exogenously formed glycation products in the potential induction of adverse health effects. Based on the available data, exogenous low molecular mass glycation products appear to be bioavailable and contribute to dicarbonyl stress and protein cross-linking, resulting in formation of endogenous AGEs. On the other hand, exogenous high molecular mass glycation products have limited bioavailability but can bind to the AGE receptor, initiating adverse health effects. Additionally, effects on gut microbiota induced by glycation products is proposed as another mode of action.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Food Science & Technology
Annick D. van den Brand, Lola Bajard, Inger-Lise Steffensen, Anne Lise Brantsaeter, Hubert A. A. M. Dirven, Jochem Louisse, Ad Peijnenburg, Sophie Ndaw, Alberto Mantovani, Barbara De Santis, Marcel J. B. Mengelers
Summary: We evaluated the exposure-health relationship of mycotoxins in humans by reviewing available literature. Since human studies did not provide clear evidence of chronic health effects, we used the AOP framework to gather mechanistic evidence from in vitro and animal studies. This evidence can support limited human studies and help identify early biomarkers of FB1 and DON.
Article
Toxicology
Aafke W. F. Janssen, Jochem Louisse, Deborah Rijkers, Nicole E. T. Pinckaers, Sjoerdtje A. Hoekstra, Ron L. A. P. Hoogenboom, Ad A. C. M. Peijnenburg, Karsten Beekmann
Summary: This study investigates the effects of per- and polyfluoroalkyl substances (PFASs) on B cells and identifies the decreased expression of RAG1 and RAG2 as potential targets in the immunotoxicity of PFASs. The concentration-response modeling analysis indicates that PFNA has the highest potency in inducing immunotoxic effects among the studied PFASs (PFNA > PFOA > PFOS > PFHxS).
ARCHIVES OF TOXICOLOGY
(2023)
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
Toxicology
Jochem Louisse, Styliani Fragki, Deborah Rijkers, Aafke Janssen, Bas van Dijk, Liz Leenders, Martijn Staats, Bas Bokkers, Marco Zeilmaker, Aldert Piersma, Mirjam Luijten, Ron Hoogenboom, Ad Peijnenburg
Summary: The aim of this study was to assess the hepatotoxicity differences of a series of PFASs using human HepaRG liver cells. The results showed that different PFASs had different effects on cellular triglyceride accumulation and gene expression. In vitro relative potency factors (RPFs) were obtained for multiple PFASs, indicating their hepatotoxic potency. The HepaRG model can be used as a screening tool for hazard and risk assessment of PFASs.
ARCHIVES OF TOXICOLOGY
(2023)