Altex-Alternatives To Animal Experimentation最新文献_第3页

Potential value of animal microphysiological systems. 动物微观生理系统的潜在价值。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-08-07 DOI: 10.14573/altex.2311141

Paul C Brown, Barry H Hooberman, Brianna L Skinner, Claudia Wrzesinski, Dayton M Petibone, Kevin A Ford, Kristi Muldoon-Jacobs, Kyung E Sung, Luis G Valerio, Nakissa N Sadrieh, Paul C Howard, Peter L Goering, Shelby A Skoog, Suzanne C Fitzpatrick, Tracy Chen, Tracy C MacGill, Donna L Mendrick

{"title":"Potential value of animal microphysiological systems.","authors":"Paul C Brown, Barry H Hooberman, Brianna L Skinner, Claudia Wrzesinski, Dayton M Petibone, Kevin A Ford, Kristi Muldoon-Jacobs, Kyung E Sung, Luis G Valerio, Nakissa N Sadrieh, Paul C Howard, Peter L Goering, Shelby A Skoog, Suzanne C Fitzpatrick, Tracy Chen, Tracy C MacGill, Donna L Mendrick","doi":"10.14573/altex.2311141","DOIUrl":"https://doi.org/10.14573/altex.2311141","url":null,"abstract":"Microphysiological systems (MPS) are designed to recapitulate aspects of tissue/organ physiology in vivo, thereby providing potential value in safety and efficacy assessments of FDA-regulated products and regulatory decision-making. While there have been significant advances in the development, use, and proposals of qualification criteria for human organ MPS, there remains a gap in the development using animal tissues. Animal MPS may be of value in many areas including the study of zoonotic diseases, assessment of the safety and efficacy of animal therapeutics, and possibly reduction of the use of animals in regulatory submissions for animal therapeutics. In addition, the development of MPS from various animal species enables comparison to animal in vivo data. This comparison, while not always critical for all contexts of use, could help gain confidence in the use and application of human MPS data for regulatory decision-making and for the potential identification of species-specific effects. The use of animal MPS is consistent with the replacement, reduction, and refinement (3Rs) principles of animal use by identifying toxic compounds before conducting in vivo studies and identifying the appropriate species for testing.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a monoclonal antibody sandwich ELISA for the determination of antigen content and quality in diphtheria vaccines. 开发用于测定白喉疫苗抗原含量和质量的单克隆抗体夹心酶联免疫吸附试验。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-07 DOI: 10.14573/altex.2305251

Laura Hassall, Daniel A Yara, Rebecca Riches-Duit, Peter Rigsby, Alexandre Dobly, Maxime Vermeulen, Antoine Francotte, Paul Stickings

{"title":"Development of a monoclonal antibody sandwich ELISA for the determination of antigen content and quality in diphtheria vaccines.","authors":"Laura Hassall, Daniel A Yara, Rebecca Riches-Duit, Peter Rigsby, Alexandre Dobly, Maxime Vermeulen, Antoine Francotte, Paul Stickings","doi":"10.14573/altex.2305251","DOIUrl":"10.14573/altex.2305251","url":null,"abstract":"At present, quality control of diphtheria vaccines by both manufacturers and national control laboratories relies heavily on in vivo assays to confirm potency. As part of the VAC2VAC project we have developed a monoclonal antibody (mAb) enzyme-linked immunosorbent assay (ELISA) to measure the relative amount and quality of diphtheria toxoid (DTxd) in diphtheria-tetanus based vaccines and believe this test has the potential to play a key role in a control strategy no longer including an in vivo potency test. The mAb ELISA is highly specific, has good dilutional linearity, and is suitable for detecting DTxd in a range of different human vaccine products. We demonstrate the ability of the assay to discriminate between batches of different content and quality using vaccine batches that were prepared to contain differing amounts of DTxd or were altered by exposure to heat or oxidative stress. We also demonstrate successful transfer of the method to other laboratories and show that different diphtheria antigen materials may be able to serve as a reference antigen for local standardization of the method. The assay is ideally suited for incorporation into a consistency approach for routine diphtheria vaccine quality control testing and may be suitable to serve as the stability indicating test in replacement of the current in vivo potency test.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"57-68"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10008309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenges integrating skin sensitization data for assessment of difficult to test substances. 整合皮肤致敏数据以评估难以测试的物质的挑战。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-10-12 DOI: 10.14573/altex.2201122

Allison Greminger, Joseph Frasca, Katy Goyak, Colin North

{"title":"Challenges integrating skin sensitization data for assessment of difficult to test substances.","authors":"Allison Greminger, Joseph Frasca, Katy Goyak, Colin North","doi":"10.14573/altex.2201122","DOIUrl":"10.14573/altex.2201122","url":null,"abstract":"Difficult to test substances, including poorly soluble, mildly irritating, or UVCBs (unknown or variable composition complex reaction products or biological materials), producing weak or borderline in vivo results, face additional challenges in in vitro assays that often necessitate data integration in a weight of evidence (WOE) approach to inform skin sensitization potential. Here we present several case studies on difficult to test substances and highlight the utility of the toxicological priority index (ToxPi) as a data visualization tool to compare skin sensitization biological activity. The case study test substances represent two poorly soluble substances, tetrakis (2-ethylbutyl) orthosilicate and decyl palmitate, and two UVCB substances, alkylated anisole and hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2 undecanone. Data from key events within the skin sensitization adverse outcome pathway were gathered from publicly available sources or specifically generated. Incorporating the data for these case study test substances as well as data on chemicals of a known sensitization class (sensitizer, irritating non-sensitizer, and non-sensitizer) into ToxPi produced biological activity profiles which were grouped using unsupervised hierarchical clustering. Three of the case study test substances concluded to lack skin sensitization potential by traditional WOE produced biological activity profiles most consistent with non-sensitizing substances, whereas the prediction was less definitive for a substance considered positive by traditional WOE. Visualizing the data using bioactivity profiles can provide further support for WOE conclusions in certain circumstances but is unlikely to replace WOE as a stand-alone prediction due to limitations of the method including the impact of missing data points.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"104-118"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41240754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developing prototypes of a modernized approach to assess crop protection chemical safety. 开发评估作物保护化学品安全性的现代化方法原型。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-31 DOI: 10.14573/altex.2307181

Richard A Currie, John Abbott, David A Dreier, Haitian Lu, Tharacad Ramanarayanan, Natalia Ryan, Odette A Watkins, Douglas C Wolf

{"title":"Developing prototypes of a modernized approach to assess crop protection chemical safety.","authors":"Richard A Currie, John Abbott, David A Dreier, Haitian Lu, Tharacad Ramanarayanan, Natalia Ryan, Odette A Watkins, Douglas C Wolf","doi":"10.14573/altex.2307181","DOIUrl":"10.14573/altex.2307181","url":null,"abstract":"In 2019, the US EPA Administrator issued a directive directing the agency away from reliance on vertebrate tests by 2035, whilst maintaining high-quality human health and environmental risk assessments. There is no accepted approach to achieve this. The decade-long duration of the crop protection (CP) chemical R&D process therefore requires both the invention and application of a modernized approach to those CP chemical projects entering corporate research portfolios by the mid-2020s. We conducted problem formulation discussions with regulatory agency scientists which created the problem statement: “Develop, demonstrate, and implement a modern scientifically sound and robust strategy that applies appropriate and flexible exposure and effects characterization without chemical specific vertebrate tests to reliably address risk, uncertainties, and deficiencies in data and its interpretation with equivalent confidence as do the currently accepted test guidelines and meet the regulatory needs of the agencies”. The solution must provide the knowledge needed to confidently conclude human health and environmental protective risk assessments. Exploring this led to a conceptual model involving the creation and parallel submission of a new approach without reliance on chemical-specific vertebrate tests. Assessment in parallel to a traditional package will determine whether it supports some, or all, of the necessary risk management actions. Analysis of any deficiencies will provide valuable feedback to focus development of tools or approaches for subsequent iterations. When found to provide sufficient information, it will form the technical foundation of stakeholder engagement to explore acceptance of a new approach to CP chemical risk assessment.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"119-130"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10148356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond Animal Testing Index: Benchmarking tool for a world beyond animal testing. 超越动物实验指数：超越动物实验世界的基准工具。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-08 DOI: 10.14573/altex.2304161

Cyrille Krul, Annick De Moor, Koen Stegmeijer, Reinout Stoop, Judith Van Luijk, Jan-Bas Prins

{"title":"Beyond Animal Testing Index: Benchmarking tool for a world beyond animal testing.","authors":"Cyrille Krul, Annick De Moor, Koen Stegmeijer, Reinout Stoop, Judith Van Luijk, Jan-Bas Prins","doi":"10.14573/altex.2304161","DOIUrl":"10.14573/altex.2304161","url":null,"abstract":"While the original definition of replacement focuses on the replacement of the use of animals in science, a more contemporary definition focuses on accelerating the development and use of predictive and robust models, based on the latest science and technologies, to address scientific questions without the use of animals. The transition to animal free innovation is on the political agenda in and outside the European Union. The Beyond Animal Testing Index (BATI) is a benchmarking instrument designed to provide insight into the activities and contributions of research institutes to the transition to animal free innovation. The BATI allows participating organizations to learn from each other and stimulates continuous improvement. The BATI was modelled after the Access to Medicine Index, which benchmarks pharmaceutical companies on their efforts to make medicines widely available in developing countries. A prototype of the BATI was field-tested with three Dutch academic medical centers and two universities in 2020-2021. The field test demonstrated the usability and effectiveness of the BATI as a benchmarking tool. Analyses were performed across five different domains. The participating institutes concluded that the BATI served as an internal as well as an external stimulus to share, learn, and improve institutional strategies towards the transition to animal free innovation. The BATI also identified gaps in the development and implementation of 3R technologies. Hence, the BATI might be a suitable instrument for monitoring the effectiveness of policies. BATI version 1.0 is ready to be used for benchmarking at a larger scale.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"69-75"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing proarrhythmic potential of environmental chemicals using a high throughput in vitro-in silico model with human induced pluripotent stem cell-derived cardiomyocytes. 使用人诱导多能干细胞衍生的心肌细胞的高通量体外计算机模型评估环境化学物质的致心律失常潜力。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-10-19 DOI: 10.14573/altex.2306231

Hsing-Chieh Lin, Ivan Rusyn, Weihsueh A Chiu

{"title":"Assessing proarrhythmic potential of environmental chemicals using a high throughput in vitro-in silico model with human induced pluripotent stem cell-derived cardiomyocytes.","authors":"Hsing-Chieh Lin, Ivan Rusyn, Weihsueh A Chiu","doi":"10.14573/altex.2306231","DOIUrl":"10.14573/altex.2306231","url":null,"abstract":"QT prolongation and the potentially fatal arrhythmia Torsades de Pointes are common causes for withdrawing or restricting drugs; however, little is known about similar liabilities of environmental chemicals. Current in vitro-in silico models for testing proarrhythmic liabilities, using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), provide an opportunity to address this data gap. These methods are still low- to medium-throughput and not suitable for testing the tens of thousands of chemicals in commerce. We hypothesized that combining high-throughput population- based in vitro testing in hiPSC-CMs with a fully in silico data analysis workflow can offer sensitive and specific predictions of proarrhythmic potential. We calibrated the model with a published hiPSC-CM dataset of drugs known to be positive or negative for proarrhythmia and tested its performance using internal cross-validation and external validation. Additionally, we used computational down-sampling to examine three study designs for hiPSC-CM data: one replicate of one donor, five replicates of one donor, and one replicate of a population of five donors. We found that the population of five donors had the best performance for predicting proarrhythmic potential. The resulting model was then applied to predict the proarrhythmic potential of environmental chemicals, additionally characterizing risk through margin of exposure (MOE) calculations. Out of over 900 environmental chemicals tested, over 150 were predicted to have proarrhythmic potential, but only seven chemicals had a MOE < 1. We conclude that a high-throughput in vitro-in silico approach using population-based hiPSC-CM testing provides a reasonable strategy to screen environmental chemicals for proarrhythmic potential.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"37-49"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Linking nanomaterial-induced mitochondrial dysfunction to existing adverse outcome pathways for chemicals. 将纳米材料诱导的线粒体功能障碍与现有的化学品不良后果途径联系起来。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-21 DOI: 10.14573/altex.2305011

Sivakumar Murugadoss, Ivana Vinković Vrček, Alexandra Schaffert, Martin Paparella, Barbara Pem, Anita Sosnowska, Maciej Stępnik, Marvin Martens, Egon L Willighagen, Tomasz Puzyn, Mihaela Roxana Cimpan, Frauke Lemaire, Birgit Mertens, Maria Dusinska, Valérie Fessard, Peter H Hoet

{"title":"Linking nanomaterial-induced mitochondrial dysfunction to existing adverse outcome pathways for chemicals.","authors":"Sivakumar Murugadoss, Ivana Vinković Vrček, Alexandra Schaffert, Martin Paparella, Barbara Pem, Anita Sosnowska, Maciej Stępnik, Marvin Martens, Egon L Willighagen, Tomasz Puzyn, Mihaela Roxana Cimpan, Frauke Lemaire, Birgit Mertens, Maria Dusinska, Valérie Fessard, Peter H Hoet","doi":"10.14573/altex.2305011","DOIUrl":"10.14573/altex.2305011","url":null,"abstract":"The adverse outcome pathway (AOP) framework plays a crucial role in the paradigm shift of toxicity testing towards the development and use of new approach methodologies. AOPs developed for chemicals are in theory applicable to nanomaterials (NMs). However, only initial efforts have been made to integrate information on NM-induced toxicity into existing AOPs. In a previous study, we identified AOPs in the AOP-Wiki associated with the molecular initiating events (MIEs) and key events (KEs) reported for NMs in scientific literature. In a next step, we analyzed these AOPs and found that mitochondrial toxicity plays a significant role in several of them at the molecular and cellular levels. In this study, we aimed to generate hypothesis-based AOPs related to NM-induced mitochondrial toxicity. This was achieved by integrating knowledge on NM-induced mitochondrial toxicity into all existing AOPs in the AOP-Wiki, which already includes mitochondrial toxicity as a MIE/KE. Several AOPs in the AOP-Wiki related to the lung, liver, cardiovascular and nervous system, with extensively defined KEs and key event relationships (KERs), could be utilized to develop AOPs that are relevant for NMs. However, the majority of the studies included in our literature review were of poor quality, particularly in reporting NM physicochemical characteristics, and NM-relevant mitochondrial MIEs were rarely reported. This study highlights the potential role of NM-induced mitochondrial toxicity in human-relevant adverse outcomes and identifies useful AOPs in the AOP-Wiki for the development of AOPs for NMs.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"76-90"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intestinal in vitro transport assay combined with physiologically based kinetic modeling as a tool to predict bile acid levels in vivo. 将肠道体外转运试验与基于生理学的动力学模型相结合，作为预测体内胆汁酸水平的工具。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-07-27 DOI: 10.14573/altex.2302011

Véronique M P De Bruijn, Willem Te Kronnie, Ivonne M C M Rietjens, Hans Bouwmeester

{"title":"Intestinal in vitro transport assay combined with physiologically based kinetic modeling as a tool to predict bile acid levels in vivo.","authors":"Véronique M P De Bruijn, Willem Te Kronnie, Ivonne M C M Rietjens, Hans Bouwmeester","doi":"10.14573/altex.2302011","DOIUrl":"10.14573/altex.2302011","url":null,"abstract":"Bile acid homeostasis is vital for numerous metabolic and immune functions in humans. The enterohepatic circulation of bile acids is extremely efficient, with ~95% of intestinal bile acids being reabsorbed. Disturbing intestinal bile acid uptake is expected to substantially affect intestinal and systemic bile acid levels. Here, we aimed to predict the effects of apical sodium-dependent bile acid transporter (ASBT)-inhibition on systemic plasma levels. For this, we combined in vitro Caco-2 cell transport assays with physiologically based (PBK) modeling. We used the selective ASBT-inhibitor odevixibat (ODE) as a model compound. Caco-2 cells grown on culture inserts were used to obtain transport kinetic parameters of glycocholic acid (GCA). The apparent Michaelis-Menten constant (Km,app), apparent maximal intestinal transport rate (Vmax,app), and ODE’s inhibitory constant (Ki) were determined for GCA. These kinetic parameters were incorporated into a PBK model and used to predict the ASBT inhibition effects on plasma bile acid levels. GCA is transported over Caco-2 cells in an active and sodium-dependent manner, indicating the presence of functional ASBT. ODE inhibited GCA transport dose-dependently. The PBK model predicted that oral doses of ODE reduced conjugated bile acid levels in plasma. Our simulations match in vivo data and provide a first proof-of-principle for the incorporation of active intestinal bile acid uptake in a bile acid PBK model. This approach could in future be of use to predict the effects of other ASBT-inhibitors on plasma and intestinal bile acid levels.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"20-36"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9911350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Why adverse outcome pathways need to be FAIR. 为什么不良结果路径需要 FAIR？

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-01 DOI: 10.14573/altex.2307131

Clemens Wittwehr, Laure-Alix Clerbaux, Stephen Edwards, Michelle Angrish, Holly Mortensen, Annamaria Carusi, Maciej Gromelski, Eftychia Lekka, Vassilis Virvilis, Marvin Martens, Luiz Olavo Bonino da Silva Santos, Penny Nymark

引用次数: 0

The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants. 体外剂量测定变化对支持吸入毒物风险评估的重要性。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-10-12 DOI: 10.14573/altex.2305311

Yvonne C M Staal, Liesbeth Geraets, Barbara Rothen-Rutishauser, Martin J D Clift, Hedwig Braakhuis, Anne S Kienhuis, Peter M J Bos

{"title":"The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants.","authors":"Yvonne C M Staal, Liesbeth Geraets, Barbara Rothen-Rutishauser, Martin J D Clift, Hedwig Braakhuis, Anne S Kienhuis, Peter M J Bos","doi":"10.14573/altex.2305311","DOIUrl":"10.14573/altex.2305311","url":null,"abstract":"In vitro methods provide a key opportunity to model human-relevant exposure scenarios for hazard identification of inhaled toxicants. Compared to in vivo tests, in vitro methods have the advantage of assessing effects of inhaled toxicants caused by differences in dosimetry, e.g., variations in concentration (exposure intensity), exposure duration, and exposure frequency, in an easier way. Variations in dosimetry can be used to obtain information on adverse effects in human-relevant exposure scenarios that can be used for risk assessment. Based on the published literature of exposure approaches using air-liquid interface models of the respiratory tract, supplemented with additional experimental data from the EU H2020 project “PATROLS” and research funded by the Dutch Ministry of Agriculture, Nature and Food Quality, the advantages and disadvantages of different exposure methods and considerations to design an experimental setup are summarized and discussed. As the cell models used are models for the respiratory epithelium, our focus is on the local effects in the airways. In conclusion, in order to generate data from in vitro methods for risk assessment of inhaled toxicants it is recommended that (1) it is considered what information really is needed for hazard or risk assessment; (2) the exposure system that is most suitable for the chemical to be assessed is chosen; (3) a deposited dose that mimics deposition in the human respiratory tract is used, and (4) the post-exposure sampling methodology should be carefully considered and relevant to the testing strategy used.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"91-103"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41240755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0