Article
Food Science & Technology
SunHwa Jeong, Seon-Mi Park, Na Rea Jo, Jin-Sook Kwon, Jimin Lee, KangMin Kim, Seon Myeong Go, Lian Cai, Dohee Ahn, Sung Duck Lee, Sang-Hwan Hyun, Kyung-Chul Choi, Eui-Bae Jeung
Summary: This study successfully improved the predictability of the developmental neurotoxicity test (DNT) method and established a second-generation discriminant function (2nd GDF) using cell assays and mobility evaluation. The results demonstrated that the method accurately classified the toxicity of the substances and showed transferability, reproducibility, and accuracy.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Food Science & Technology
Antonio Hernandez-Jerez, Paulien Adriaanse, Annette Aldrich, Philippe Berny, Tamara Coja, Sabine Duquesne, Andreas Focks, Marina Marinovich, Maurice Millet, Olavi Pelkonen, Silvia Pieper, Aaldrik Tiktak, Christopher Topping, Anneli Widenfalk, Martin Wilks, Gerrit Wolterink, Kevin Crofton, Susanne Hougaard Bennekou, Martin Paparella, Ioanna Tzoulaki
Summary: The EFSA Panel on Plant Protection Products and their Residues conducted two AOP-informed IATA case studies to address the DNT hazard identification and characterisation problem for pesticide active substances deltamethrin and flufenacet. Through systematic literature review, expert knowledge elicitation, and probabilistic approach, the studies explored the applicability of the DNT in vitro testing battery in regulatory risk assessment. This evidence-based approach allowed for conclusions with an acceptable level of certainty in DNT hazard identification and characterisation.
Review
Physiology
Josele Flores-Santin, Warren W. Burggren
Summary: While the chicken is a widely used animal model in biomedical research, its high level of specialization may affect the generalizability of experimental results. Therefore, researchers should explore alternative bird models to expand developmental studies.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Monika Wieser, Stefanie Burger, Reinhard Ertl, Stefan Kummer, Melanie Stargardt, Ingrid Walter
Summary: This study conducted a process validation on the freezing of tissue samples, demonstrating that freezing in liquid nitrogen provides samples suitable for RNA investigations. It also observed a negative impact on the RIN value of liver samples.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Isabelle Matias, Ilaria Belluomo, Pierre-Louis Raux, Monique Vallee
Summary: The emergence of metabolomics and quantification approaches has allowed for the discovery of new biomarkers for drug development. Tandem mass spectrometry is the preferred method for this, but it requires a specific validation process for both preclinical and clinical applications. Research on lipid mediators, specifically steroids and cannabinoids, has revealed a potential link to cannabis addiction and metabolism-related disorders. In this study, we developed GC-MS/MS and LC-MS/MS methods for routine quantification of targeted steroids and cannabinoids. Our methods showed satisfactory results for most validation conditions, although not all analytes met the acceptance criteria. Our validation process met the standards for GLP-qualified methods, allowing for routine analytical studies in preclinical and clinical settings.
Review
Veterinary Sciences
Lewis B. Kinter, David K. Johnson, Robert H. Weichbrod, Ernest D. Prentice, Richard C. Simmonds, Paul W. Houghton, Robert A. Whitney, Joseph DeGeorge, W. Ron DeHaven, Klaas Kramer, Louis DeTolla
Summary: The organization and function of the institutional animal care and use committee (IACUC) plays a crucial role in scientific research involving live animals and animal care programs. The roles and responsibilities of IACUCs have evolved to include scientific quality, data reproducibility, and animal welfare as essential components of generating new knowledge and medical treatments.
Article
Mathematics
Haitham M. Yousof, Hafida Goual, Walid Emam, Yusra Tashkandy, Morad Alizadeh, M. Masoom Ali, Mohamed Ibrahim
Summary: This paper presents a new extension of the exponential distribution, focusing on the practical application of the model. Six different classical estimation methods are compared and evaluated using four sets of data. Additionally, four applications are described along with the derivation of the new Nikulin statistic test for the new probability model under censored situation. Simulation experiments are conducted to evaluate the tests on complete, artificial, and censored data. Furthermore, a set of simulation experiments is used to evaluate the original statistical test and a new modified statistical test based on statistical controls in the evaluation processes.
Article
Biochemical Research Methods
Yang Zhao, Estatira Sepehr, Cory Vaught, Jeffrey Yourick, Robert L. Sprando
Summary: Several cannabinoids and ethanol hemp extract were studied for their toxicological mechanisms, oromucosal absorption, and metabolites using human hepatocytes, C. elegans, and in vitro buccal membrane absorption models. A UHPLC-ESI-MS/MS method was developed to quantify the cannabinoids in extracellular matrices, and it exhibited good linearity, precision, and accuracy. The method also avoided time-consuming sample preparation.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Chemistry, Applied
Veronica Maria Teresa Lattanzio, Biancamaria Ciasca, Emanuela Verdini, Christoph von Holst, Ivan Pecorelli
Summary: The design, execution and evaluation of an interlaboratory validation study for a LC-MS/MS method used in detecting polar pesticides in animal-derived food are reported. The study involved five participant laboratories who were asked to analyze test samples contaminated with 11 polar pesticides. The method showed high average recoveries and good repeatability and reproducibility, providing insights for its implementation by new users.
FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT
(2023)
Article
Cell Biology
Leyre Echeazarra, Gontzal Garcia del Cano, Sergio Barrondo, Imanol Gonzalez-Burguera, Miquel Saumell-Esnaola, Xabier Aretxabala, Maider Lopez de Jesus, Leire Borrega-Roman, Susana Mato, Catherine Ledent, Carlos Matute, Maria Aranzazu Goicolea, Joan Salles
Summary: This study identifies specific anti-CB1 antibodies for particular research purposes, highlighting the importance of proper validation before use. The research shows that different antibodies may behave differently in various assays, indicating a need for tailored antibody selection based on specific experimental requirements. These results provide valuable insights for interpreting past and future research results involving anti-CB1 antibodies.
HISTOCHEMISTRY AND CELL BIOLOGY
(2021)
Article
Biochemical Research Methods
Catherine E. DelGuidice, Omnia A. Ismaiel, William R. Mylott, Moucun Yuan, Matthew S. Halquist
Summary: This manuscript describes the development and validation of an LC-HRMS method for the quantitative analysis of Ranibizumab and Bevacizumab in human vitreous and aqueous humor. The optimized method provides a proof-of-concept template for challenging bioanalytical techniques and offers valuable efficacy information for these drugs.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Jakob Valtl, Ullrich J. Moenich, Desmond S. Lun, James Kelley, Catherine M. Grgicak
Summary: This paper discusses various methods for estimating the number of contributors in complex DNA mixtures, comparing two exemplar NOC systems: a Bayesian system (NOCIt) and an artificial neural network (ANN). The Bayesian method offers a more sensitive and specific probability distribution, while the ANN method is faster and more repeatable. Validation and testing of NOC systems will need to consider the specific needs of forensic laboratories, whether they require a single estimate or a range of estimates for contributor numbers.
FORENSIC SCIENCE INTERNATIONAL-GENETICS
(2021)
Article
Biochemical Research Methods
Akanksha Goyal, Maria Hauswald, Helen McCallum, Gerald Hoebarth, Annette Feussner
Summary: A modified biotin-drug extraction and acid dissociation (BEAD) immunogenicity assay was developed to detect anti-drug-antibodies (ADA) against the human anti-FXIIa monoclonal antibody (mAb) drug, Garadacimab (previously called CSL312). The assay showed high drug tolerance and sensitivity in line with FDA guidelines. Validation in a repeat-dose animal safety study confirmed its acceptability, although the inter-assay precision was lower. The assay was deemed fit-for-purpose in the nonclinical study context.
JOURNAL OF IMMUNOLOGICAL METHODS
(2023)
Article
Pharmacology & Pharmacy
Roland Lawson, Sophie Leymarie, Claire Nikitopoulos, Antoine Humeau, Hichem Bouchenaki, Jean-Luc Duroux, Laurent Fourcade, Sandrine Karam, Nicolas Picard, Claire Demiot
Summary: This study aimed to assess whether digital tools could replace live animal experiments in terms of motivation and knowledge acquisition. The results showed that digital pedagogical tools were well accepted by students and were equivalent to traditional teaching methods in terms of motivation and knowledge acquisition.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2022)
Article
Pathology
Brad Bolon, Lori A. Dostal, Robert H. Garman
Summary: The developmental neuropathology examination in juvenile toxicity studies varies depending on the nature of the product candidate, its intended use, and the exposure scenario. Expectations for sampling, processing, and evaluating neural tissues differ for developmental neurotoxicity studies for chemicals and juvenile animal studies for pediatric pharmaceuticals.
TOXICOLOGIC PATHOLOGY
(2021)
Article
Reproductive Biology
Philip Marx-Stoelting, Marize de L. M. Solano, Hiroaki Aoyama, Ralf H. Adams, Anna Bal-Price, Jochen Buschmann, Ibrahim Chahoud, Ruth Clark, Tian Fang, Michio Fujiwara, Michael Gelinsky, Konstanze Grote, Masao Horimoto, Susanne Hougaard Bennekou, Rupert Kellner, Makiko Kuwagata, Marcel Leist, Annemarie Lang, Weihua Li, Alberto Mantovani, Susan L. Makris, Francisco Paumgartten, Monique Perron, Magdalini Sachana, Anne Schmitt, Steffen Schneider, Gilbert Schoenfelder, Frank Schulze, Kohei Shiota, Roland Solecki
Summary: The 10th Berlin Workshop aimed to discuss scientific, methodologic and regulatory aspects in risk assessment of developmental toxicity and to debate alternative strategies in testing developmental effects in the future. Recommendations for improvement of categorization, database update, and development of adverse outcome pathways related to DNT were discussed. Collaboration with the medical community was suggested to enhance relevance of test results to humans and accelerate the development of new technologies for identifying developmental health risks.
REPRODUCTIVE TOXICOLOGY
(2021)
Article
Toxicology
Johannes Delp, Andrea Cediel-Ulloa, Ilinca Suciu, Petra Kranaster, Barbara M. A. van Vugt-Lussenburg, Vesna Munic Kos, Wanda van der Stel, Giada Carta, Susanne Hougaard Bennekou, Paul Jennings, Bob van de Water, Anna Forsby, Marcel Leist
Summary: The study utilized 21 pesticides described as mitochondrial inhibitors to investigate the adverse outcome pathway (AOP:3) of Parkinson's disease, finding that some inhibitors triggered neurodegeneration while others did not. There was a clear hierarchy of assay sensitivity, with mitochondrial failure being much more sensitive than neurite damage in predicting toxic reactions.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Toxicology
Dominik Loser, Maria G. Hinojosa, Jonathan Blum, Jasmin Schaefer, Markus Bruell, Ylva Johansson, Ilinca Suciu, Karin Grillberger, Timm Danker, Clemens Moeller, Iain Gardner, Gerhard F. Ecker, Susanne H. Bennekou, Anna Forsby, Udo Kraushaar, Marcel Leist
Summary: The study demonstrates that several neonicotinoid pesticides can trigger human neuronal signaling at low micromolar concentrations, raising concerns about their potential impact on nervous system development.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Food Science & Technology
Simon More, Vasileios Bampidis, Diane Benford, Claude Bragard, Thorhallur Halldorsson, Susanne Hougaard Bennekou, Kostas Koutsoumanis, Kyriaki Machera, Hanspeter Naegeli, Soren Nielsen, Josef Schlatter, Dieter Schrenk, Vittorio Silano, Dominique Turck, Maged Younes, Peter Aggett, Jacqueline Castenmiller, Alessandra Giarola, Agnes De Sesmaisons-Lecarre, Jose Tarazona, Hans Verhagen, Antonio Hernandez-Jerez
Summary: This Statement proposes a harmonised approach for establishing Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients, outlining specific considerations and a decision tree for risk characterisation. It recommends involving relevant EFSA Panels and units for integrated hazard and risk characterisation of regulated products that are also nutrients.
Article
Food Science & Technology
Simon More, Vasileios Bampidis, Diane Benford, Claude Bragard, Thorhallur Halldorsson, Antonio Hernandez-Jerez, Susanne Hougaard Bennekou, Kostas Koutsoumanis, Claude Lambre, Kyriaki Machera, Hanspeter Naegeli, Soren Nielsen, Josef Schlatter, Dieter Schrenk, Vittorio Silano, Dominique Turck, Maged Younes, Jacqueline Castenmiller, Qasim Chaudhry, Francesco Cubadda, Roland Franz, David Gott, Jan Mast, Alicja Mortensen, Agnes G. Oomen, Stefan Weigel, Eric Barthelemy, Ana Rincon, Jose Tarazona, Reinhilde Schoonjans
Summary: The updated EFSA Guidance focuses on risk assessment of nanoscience and nanotechnologies in the food and feed chain, human and animal health. It covers relevant scientific studies, physico-chemical properties, exposure assessment, and hazard characterization of nanomaterials in various application areas. Specific details on physico-chemical characterization, key parameters measurement, methods and techniques, exposure assessment, hazard identification and characterisation, toxicological studies, and risk characterisation are provided in the updated guidance.
Article
Food Science & Technology
Antonio Hernandez-Jerez, Paulien Adriaanse, Annette Aldrich, Philippe Berny, Tamara Coja, Sabine Duquesne, Andreas Focks, Marina Marinovich, Maurice Millet, Olavi Pelkonen, Silvia Pieper, Aaldrik Tiktak, Christopher Topping, Anneli Widenfalk, Martin Wilks, Gerrit Wolterink, Kevin Crofton, Susanne Hougaard Bennekou, Martin Paparella, Ioanna Tzoulaki
Summary: The EFSA Panel on Plant Protection Products and their Residues conducted two AOP-informed IATA case studies to address the DNT hazard identification and characterisation problem for pesticide active substances deltamethrin and flufenacet. Through systematic literature review, expert knowledge elicitation, and probabilistic approach, the studies explored the applicability of the DNT in vitro testing battery in regulatory risk assessment. This evidence-based approach allowed for conclusions with an acceptable level of certainty in DNT hazard identification and characterisation.
Review
Biochemistry & Molecular Biology
Yusuke Oku, Federica Madia, Pierre Lau, Martin Paparella, Timothy McGovern, Mirjam Luijten, Miriam N. Jacobs
Summary: With the recent rapid advancement of methodological tools, the mechanistic understanding of biological processes leading to carcinogenesis is expanding. New methodologies such as transcriptomics can provide information on non-genotoxic mechanisms of chemical carcinogens for regulatory applications. The OECD expert group is reviewing assays to be integrated into the Integrated Approach to the Testing and Assessment (IATA) of Non-Genotoxic Carcinogens (NGTxC), focusing on pre-screening gene expression changes associated with phenotypic alterations that underlie carcinogenic processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Environmental Sciences
Laura M. Langan, Martin Paparella, Natalie Burden, Lisa Constantine, Luigi Margiotta-Casaluci, Thomas H. Miller, S. Jannicke Moe, Stewart F. Owen, Alexandra Schaffert, Tiina Sikanen
Summary: This article reviews the current level of knowledge around nonanimal testing methods for hazard and exposure assessment, and environmental and health risks of pharmaceuticals and personal care products in the natural environment. It highlights advancements in aquatic environmental risk assessment and emphasizes the need for a global and inclusive approach to establish consensus for regulatory assessment and decision-making.
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
(2023)
Letter
Medicine, Research & Experimental
Alexandra Schaffert, Sivakumar Murugadoss, Birgit Mertens, Martin Paparella
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2023)
Article
Medicine, Research & Experimental
Veera Hautanen, Tarja Toimela, Martin Paparella, Tuula Heinonen
Summary: The induction of vasculature formation is proposed as a significant mechanism for the non-genotoxic carcinogenicity of a chemical. This study developed an assay using a coculture model of human primary HUVECs and hASCs to assess vasculature formation induction. Different assay protocols were compared to identify the optimal conditions, and essential serum supplements and growth factors were identified. Certain chemicals were found to induce vasculature formation, indicating the potential use of this human cell-based assay as a test for non-genotoxic carcinogenicity.
ATLA-ALTERNATIVES TO LABORATORY ANIMALS
(2023)
Review
Biochemistry & Molecular Biology
Annamaria Colacci, Raffaella Corvi, Kyomi Ohmori, Martin Paparella, Stefania Serra, Iris Da Rocha Carrico, Paule Vasseur, Miriam Naomi Jacobs
Summary: This article describes the history of the development of cell transformation assays (CTAs), providing an overview from their origin to the new transcriptomic-based CTAs. The application of this knowledge is used to address how different types of CTAs can be included in the integrated approach to testing and assessment (IATA) for non-genotoxic carcinogens. The article also discusses how different CTA models fit into the preceding steps of the IATA, and maps complementary key biomarkers to represent the complexity of (non-genotoxic) carcinogenesis process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Toxicology
Miriam N. N. Jacobs, Jan M. M. Bult, Kevin Cavanagh, Christophe Chesne, Nathalie Delrue, Jianan Fu, Emma Grange, Ingrid Langezaal, Dominika Misztela, Jenny Murray, Martin Paparella, Gilly Stoddart, Torsten Tonn, Carol Treasure, Masaaki Tsukano, Rosemary Versteegen
Summary: The ethical concerns and needs regarding the use and sourcing of human materials, especially serum, in OECD in vitro test guidelines were explored in an international workshop held in 2019. The workshop examined health-related aspects of the donation procedure, supply and availability of serum, and traceability of serum for the Test Guideline Programme. Recommendations including informed donor consent, human serum information requirements, and suitable sources for serum were provided to ensure ethical practices and avoid competition in supply.
FRONTIERS IN TOXICOLOGY
(2023)
Meeting Abstract
Toxicology
S. H. Bennekou
TOXICOLOGY LETTERS
(2021)
Article
Food Science & Technology
Simon More, Vasileios Bampidis, Diane Benford, Claude Bragard, Thorhallur Halldorsson, Antonio Hernandez-Jerez, Susanne Hougaard Bennekou, Kostas Koutsoumanis, Kyriaki Machera, Hanspeter Naegeli, Soren Saxmose Nielsen, Josef Schlatter, Dieter Schrenk, Vittorio Silano, Dominique Turck, Maged Younes, Gerard Arnold, Jean-Lou Dorne, Angelo Maggiore, Stephen Pagani, Csaba Szentes, Simon Terry, Simone Tosi, Domagoj Vrbos, Giorgia Zamariola, Agnes Rortais
Summary: The study proposes a holistic risk assessment approach for multiple stressors in honey bees, with a focus on monitoring and modeling systems. Systematic data collection on bee health, chemical residues, and surrounding landscapes will inform stakeholders and support the development of environmental risk assessments.
Article
Medicine, Research & Experimental
Martin Paparella, Stefan Scholz, Scott Belanger, Thomas Braunbeck, Pascal Bicherel, Kristin Connors, Christopher Fassbender, Marlies Halder, Adam Lillicrap, Roman Liska, Kristin Schirmer, Gilly Stoddart, Paul Thomas, Susanne Walter-Rohde
Summary: This research summarizes the limitations and uncertainties of TG 203, emphasizing the need for combining this method with alternative methods to achieve better environmental protection. It points out the importance of environmental safety extrapolation and the potential for higher throughput assessment of chemicals with the use of alternative methods.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2021)
Article
Reproductive Biology
Lei Gong, Siyi Jiang, Jia Tian, Yong Li, Wansu Yu, Lubo Zhang, Daliao Xiao
Summary: Exposure to gestational diabetes mellitus during pregnancy can lead to the development of a neonatal brain hypoxia/ischemia-sensitive phenotype. The PTEN/AKT/mTOR/autophagy signaling pathway plays a role in this process.
REPRODUCTIVE TOXICOLOGY
(2024)
Article
Reproductive Biology
Sudipta Dutta, Kirthiram K. Sivakumar, John W. Erwin, Jone A. Stanley, Joe A. Arosh, Robert J. Taylor, Sakhila K. Banu
Summary: This study found that exposure to hexavalent chromium disrupts follicle development and causes apoptosis by altering epigenetic marks in the ovary.
REPRODUCTIVE TOXICOLOGY
(2024)
Article
Reproductive Biology
Yuxin Li, Xianzhi He, Bin Sun, Nannan Hu, Jiamin Li, Ruolan You, Feiyan Tao, Lei Fang, Yuanyuan Li, Qingfeng Zhai
Summary: This study investigated the toxic effects and mechanism of beta-CYP and EMB on the reproductive system of female rats. The results showed that exposure to these pesticides led to changes in hormone and gene expression in the hypothalamic-pituitary-ovarian axis, as well as alterations in oxidative damage indicators. The findings support the evaluation of the adverse effects of pesticide exposure on reproductive health in greenhouse operations.
REPRODUCTIVE TOXICOLOGY
(2024)
Article
Reproductive Biology
Ran Lee, Won-Young Lee, Hyun-Jung Park
Summary: This study investigates the toxicity of diuron on fetal mouse testes and finds that diuron has a negative impact on the development of fetal Leydig cells, while not affecting germ cells and Sertoli cells.
REPRODUCTIVE TOXICOLOGY
(2024)