ALTEX最新文献 - Book学术

Material-mediated pyrogens in medical devices: Myth or reality? 医疗器械中物质介导的热原：神话还是现实？

ALTEX Pub Date : 2025-07-09 DOI: 10.14573/altex.2504231

Lindsey Borton, Kelly Coleman

{"title":"Material-mediated pyrogens in medical devices: Myth or reality?","authors":"Lindsey Borton, Kelly Coleman","doi":"10.14573/altex.2504231","DOIUrl":"https://doi.org/10.14573/altex.2504231","url":null,"abstract":"Annex G of ISO 10993-11:2017 lists 24 substances that are allegedly material-mediated pyrogens (MMPs) in medical devices and recommends using the rabbit pyrogen test (RPT) for MMP evaluation. We aimed to establish whether medical devices contain MMPs; determine if MMPs are pyrogens or uncouplers of oxidative phosphorylation (UOPs); complete a survey of RPT failures; and develop a UOP screening list. A literature search was conducted to identify MMPs associated with medical devices. Concurrently, data mining was conducted to search for MMPs in medical device extractables databases and collect RPT data from industry and contract research labs. The literature search produced the conclusions: (1) Annex G's endogenous biological compounds are pyrogenic; (2) Annex G's drugs and UOP substances are not pyrogenic but thermogenic; (3) numerous other UOPs were identified; and (4) nearly all UOPs are poorly soluble in saline (the RPT's injection solvent). The data mining found two Annex G MMPs in medical device extracts that were not pyrogenic and confirmed that the RPT failure rate was low, with investigated failures caused by endotoxin or test incompatibilities, not by Annex G MMPs. Since no pyrogenic Annex G MMPs or saline soluble UOPs were found in medical device extracts, the RPT is unnecessary. If UOPs are detected during chemical characterization studies, an ISO 10993-17:2023 toxicological risk assessment can be used to determine their hazard potential. Residual biological contamination can be evaluated with the human monocyte activation test, which detects all biological pyrogens. The term \"MMP\" is inaccurate and obsolete.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical selection for the Thyroid Validation Study coordinated by EURL ECVAM and involving EU-NETVAL laboratories. 由EURL ECVAM协调并涉及EU-NETVAL实验室的甲状腺验证研究的化学选择。

ALTEX Pub Date : 2025-07-07 DOI: 10.14573/altex.2501152

Camilla Bernasconi, Stavroula Sampani, Anna Beronius, Sandra Coecke, Ingrid Langezaal, Francesca Pistollato, Alicia Paini, Amalia Muñoz, David Asturiol, Aude Kienzler, Giovanna Baron, Sharon Munn, Helena Kandarova, Maurice Whelan

{"title":"Chemical selection for the Thyroid Validation Study coordinated by EURL ECVAM and involving EU-NETVAL laboratories.","authors":"Camilla Bernasconi, Stavroula Sampani, Anna Beronius, Sandra Coecke, Ingrid Langezaal, Francesca Pistollato, Alicia Paini, Amalia Muñoz, David Asturiol, Aude Kienzler, Giovanna Baron, Sharon Munn, Helena Kandarova, Maurice Whelan","doi":"10.14573/altex.2501152","DOIUrl":"https://doi.org/10.14573/altex.2501152","url":null,"abstract":"The aim of the Thyroid Validation Study, coordinated by EURL ECVAM and involving EU-NETVAL laboratories, was to validate selected non-animal methods for the identification of chemicals that can potentially disrupt the thyroid hormone system in humans. The validation study was organized in two parts: Part 1 was to assess method performance and develop standard operating procedures, where needed, and Part 2 was to assess the mechanistic relevance of the methods using a set of validation chemicals. This paper describes the stepwise process to select this validation set of chemicals, mainly based on extensive literature review and expert judgment elicitation to identify chemicals for which there was evidence to show their (lack of) ability to perturb the thyroid hormone signaling mechanisms or modes of action covered by the methods. A unique contribution of the study lies in its mechanistic coverage of molecular targets within the thyroid gland but also regulatory mechanisms in peripheral tissues, reflecting a multifaceted perspective on thyroid hormone action. The validation set consisted of 30 chemicals, providing a balanced representation across a broad chemical space and offering insights into the mechanistic relevance of the selected methods. Once validated, these methods will contribute to advancing the identification and evaluation of endocrine disruptors, informing regulatory decisions, and promoting alternative testing strategies.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ways to broaden the awareness, consideration and adoption of new approach methodologies (NAMs). 如何扩大对新方法方法的认识、考虑和采用。

ALTEX Pub Date : 2025-06-26 DOI: 10.14573/altex.2505281

Oluwakemi Oyetade, David G Allen, Jessie Carder, Elizabeth A Farley-Dawson, Emily Reinke, Shannon Marko, Nicole C Kleinstreuer, Helena T Hogberg

{"title":"Ways to broaden the awareness, consideration and adoption of new approach methodologies (NAMs).","authors":"Oluwakemi Oyetade, David G Allen, Jessie Carder, Elizabeth A Farley-Dawson, Emily Reinke, Shannon Marko, Nicole C Kleinstreuer, Helena T Hogberg","doi":"10.14573/altex.2505281","DOIUrl":"https://doi.org/10.14573/altex.2505281","url":null,"abstract":"New approach methodologies (NAMs) refer to any technology, methodology, or combination thereof used to inform on chemical hazard and risk, and support replacement, reduction, or refinement of animal use. While the development and application of NAMs has recently increased, their adoption in regulatory decisions is slow and awareness outside the community is low. The Consideration of Alternative Methods Working Group (CAMWG) within the Interagency Coordinating Committee on the Validation of Alternative Methods focused on understanding how NAMs are considered by stakeholders and identifying ways to encourage adoption. A set of questions was developed to focus stakeholder discussions; CAMWG members met with stakeholder representatives to collect perspectives on how alternatives to traditional animal tests are considered when developing toxicology testing and research programs. Participants represented agrochemical, industrial chemical, consumer products, and pharmaceutical companies; academic researchers in toxicology; and Institutional Animal Care and Use Committees. All stakeholders currently use or consider NAMs-some more than others. Challenges to broader NAM adoption were identified and five common themes emerged as potential barriers: perception, regulatory acceptance, scientific and technical limitations, education, and financial considerations. Solutions to overcoming barriers were identified, such as tailored education, proactive collaboration and improved communication. Additional recommendations were ensuring fit-for-purpose use of NAMs, developing harmonized national and global acceptance criteria, identifying funding sources, increasing awareness about NAMs strengths and limitations, and a need for a more central repository for NAMs information. Here, we detail these discussions about NAMs use, barriers, and proposed solutions, to successfully expand awareness, consideration, and adoption.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of the publication rate of recent research projects using non-human primates in France. 法国最近使用非人类灵长类动物的研究项目发表率的调查。

ALTEX Pub Date : 2025-06-23 DOI: 10.14573/altex.2501292

Roland Cash, Lilas Courtot

{"title":"Investigation of the publication rate of recent research projects using non-human primates in France.","authors":"Roland Cash, Lilas Courtot","doi":"10.14573/altex.2501292","DOIUrl":"https://doi.org/10.14573/altex.2501292","url":null,"abstract":"The use of non-human primates (NHPs) in biomedical research entails significant ethical considerations, demanding careful evaluation of both scientific necessity and research outcomes. This study presents a retrospective literature review comparing non-technical summaries (NTS) of research projects authorized in France between 2016 and mid-2019 with corresponding peer-reviewed scientific publications. The primary objective was to assess the publication rate of NHP-based projects, with secondary outcomes including time to publication, discrepancy in animal use reporting, and the scientific impact of published results. Literature searches were conducted primarily via PubMed, supplemented with additional methods such as author-based searches. Out of 191 projects analyzed, 56% led to at least one publication, the publication rate varying markedly, ranging from 83% in ophthalmology to 30% in immunology. In most cases, publications reported fewer animals than originally authorized: 1,751 actually used out of the 3,649 planned. 2,421 animals had been authorized for the projects for which no publication could be identified. The overall median Relative Citation Ratio (RCR), representing the field- and time-normalized citation rate for published studies, was 1.1, indicating a moderate scientific impact. These findings highlight the need for greater transparency in reporting, including the publication of negative or inconclusive results. The study underscores the importance of systematic retrospective assessments, improved harm/benefit evaluations under the EU Directive, and stronger upstream review mechanisms. Key recommendations include pre-registration of studies, mandated publication of all research outcomes, and the development of open-access platforms to facilitate data sharing, reduce unnecessary duplication, and enhance both ethical and scientific value.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Estimation of bioavailable concentration of endogenously formed N-nitrosamines by physiologically based kinetic modelling. 基于生理动力学模型的内源性n -亚硝胺生物可利用浓度估算。

ALTEX Pub Date : 2025-06-23 DOI: 10.14573/altex.2412061

Max Spaenig, Matthias Vogel, Tanja Hansen, Leroy Elenschneider, Anke Londenberg, Rhys Whomsley, Uwe Deppenmeier, Sylvia E Escher

{"title":"Estimation of bioavailable concentration of endogenously formed N-nitrosamines by physiologically based kinetic modelling.","authors":"Max Spaenig, Matthias Vogel, Tanja Hansen, Leroy Elenschneider, Anke Londenberg, Rhys Whomsley, Uwe Deppenmeier, Sylvia E Escher","doi":"10.14573/altex.2412061","DOIUrl":"https://doi.org/10.14573/altex.2412061","url":null,"abstract":"N-nitrosamines (NAs) are potentially carcinogenic organic compounds, and nitrosamine drug substance-related impurities (NDSRIs) are currently regulated with class-specific thresholds in the low nanogram range according to the carcinogenic potency categorization approach (CPCA) classification schema. Beyond direct exposure, NDSRIs can form endogenously in the human organism after ingestion of secondary amines. As recently shown, enalapril, propranolol, and fluoxetine form NDSRIs under conditions mimicking the acidic environment in the stomach. The MUTAMIND project investigated whether such endogenously formed NA levels lead to plasma or liver concentrations which align with or exceed the acceptable intake limits based on the current CPCA. A generic physiologically based kinetic (PBK) model was built using compound-specific in vitro ADME parameters such as intestinal permeability and hepatic clearance. The predictions correlated well with measured in vivo ADME data for the data-rich APIs, so the same PBK approach was applied to the corresponding NDSRIs. While the modelling of propranolol was unremarkable, the highest NA conversion rate observed for N-nitrosoenalapril under gastric conditions resulted in plasma and liver levels exceeding those derived from the CPCA threshold by a factor of about 800 and 400, respectively. The long half-life of fluoxetine suggests a risk of bioaccumulation of its nitrosamine with chronic exposure. These findings indicate that PBK modelling could be a valuable tool as part of a weight of evidence approach in contributing to the risk assessment of nitrosamine impurities in pharmaceuticals.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of a high-throughput in-vitro-to-in-vivo extrapolation (IVIVE) workflow for the prioritization of potential developmental toxicity of chemicals. 评估高通量体外到体内外推（IVIVE）工作流程，以确定化学品潜在发育毒性的优先级。

ALTEX Pub Date : 2025-05-28 DOI: 10.14573/altex.2406281

Matthew W Linakis, Rebecca A Clewell, Jerry Campbell, P Robinan Gentry, Harvey J Clewell

{"title":"Evaluation of a high-throughput in-vitro-to-in-vivo extrapolation (IVIVE) workflow for the prioritization of potential developmental toxicity of chemicals.","authors":"Matthew W Linakis, Rebecca A Clewell, Jerry Campbell, P Robinan Gentry, Harvey J Clewell","doi":"10.14573/altex.2406281","DOIUrl":"https://doi.org/10.14573/altex.2406281","url":null,"abstract":"New approach methodologies (NAMs) are rapidly being developed to help improve the speed of risk assessment and reduce the use of animals. In vitro to in vivo extrapolation (IVIVE) is necessary to translate NAM data to human exposures. While past IVIVE efforts have demonstrated impressive success, several specialized scenarios exist where current IVIVE methods have not been tested, including pregnancy and developmental toxicity. To that end, this investigation proposes a preliminary IVIVE workflow for identification of potential developmental toxicants. Readily available in vitro and in vivo data with developmental toxicity endpoints were aggregated from the US Environmental Protection Agency's CompTox Chemicals Dashboard. In vitro distribution models (i.e. Armitage model) and both generic (httk) and bespoke physiologically-based pharmacokinetic (PBPK) models were used to estimate exposures from blood concentrations associated with in vitro bioactivity (reverse dosimetry) and NAM-based bioactive doses were compared to in vivo endpoints (LOAELs) where available. Based on literature sources, this method identified chemicals as a high, medium, or low priority for follow-up as a developmental toxicant. Of the 23 chemicals with in vitro developmental toxicity assays, 7 had a NAM-based human oral equivalent dose (hOED) that was lower for developmental assays than for all available assays, indicating that the use of all in vitro data to derive a hOED would generally provide the most conservative approach. Potential data streams and refinements for improvement of the IVIVE workflow are also discussed.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Determination of U-SENS™ borderline range thresholds to address uncertainty for skin sensitization assessment in a regulatory context. 确定U-SENS™边界范围阈值，以解决监管环境下皮肤致敏评估的不确定性。

ALTEX Pub Date : 2025-05-23 DOI: 10.14573/altex.2411282

Laurent Nardelli, Fleur Tourneix, Leopold Carron, Erwin van Vliet, Nathalie Alépée

{"title":"Determination of U-SENS™ borderline range thresholds to address uncertainty for skin sensitization assessment in a regulatory context.","authors":"Laurent Nardelli, Fleur Tourneix, Leopold Carron, Erwin van Vliet, Nathalie Alépée","doi":"10.14573/altex.2411282","DOIUrl":"https://doi.org/10.14573/altex.2411282","url":null,"abstract":"Skin sensitization is an endpoint in the safety evaluation of chemicals. OECD guideline 497 includes three defined approaches (DAs) integrating new approach methodologies (NAMs) for skin sensitization hazard identification or UN GHS potency categorization. The \"2 out of 3\" (2o3) DA predicts skin sensitization hazard by sequentially testing in up to three NAMs covering key events (KEs) 1-3 of the adverse outcome pathway (AOP). To increase flexibility, OECD is considering the adoption of \"alternate\" NAMs in guideline 497 targeting the same AOP KE as in test guidelines 442C, 442D, 442E. This study evaluated the feasibility of substituting the h-CLAT with U-SENS™ in the 2o3 DA as NAM for AOP KE 3. To define areas where uncertainty may exist in U-SENS™ predictions, borderline range thresholds around the 150% CD86 stimulation index (SI) cut-off were calculated using a log pooled median absolute deviation method. A revised U-SENS™ prediction model implementing these thresholds classifies a chemical as positive (SI > 176%), negative (SI < 128%), or borderline (128 ≤ SI ≤ 176%). Application of the model changed the U-SENS™ predictions for 35 of 191 chemicals in the OECD database. Substituting the h-CLAT with U-SENS™ in the 2o3 DA resulted in a balanced accuracy of 71% against LLNA (n=168) and 77% against human data (n=66), without considering borderline range thresholds. Incorporating thresholds improved the balanced accuracy to 77% (LLNA, n=142) and 88% (human, n=55). These findings support the inclusion of the U-SENS™ and its borderline range thresholds in OECD guideline 497.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KoCVAM-led validation of KeraSkin™ Phototoxicity Assay for inclusion in OECD TG 498. kocvam主导的KeraSkin™光毒性测定法的验证，用于OECD TG 498。

ALTEX Pub Date : 2025-05-23 DOI: 10.14573/altex.2407041

Nam-Hee Kang, Chang-Eon Park, So-Hee Kim, Eunji Gwak, Seongsook Kim, Min-Gyu Go, Joohwan Kim, Sun-Wook Woo

{"title":"KoCVAM-led validation of KeraSkin™ Phototoxicity Assay for inclusion in OECD TG 498.","authors":"Nam-Hee Kang, Chang-Eon Park, So-Hee Kim, Eunji Gwak, Seongsook Kim, Min-Gyu Go, Joohwan Kim, Sun-Wook Woo","doi":"10.14573/altex.2407041","DOIUrl":"https://doi.org/10.14573/altex.2407041","url":null,"abstract":"Phototoxicity (or photoirritation) is defined as an acute toxic response elicited by topically or systematically administered photoreactive chemicals after the exposure of the body to environmental light. Korean Center for the Validation of Alternative Methods (KoCVAM) developed and optimized an in vitro phototoxicity test method using KeraSkin™, a reconstructed human epidermis model (RhE), (KeraSkin™ Phototoxicity Assay) as a 'me-too' test method in a previous study. KeraSkin™ Phototoxicity Assay was added to the OECD Workplan for inclusion in OECD test guideline (TG) 498. This study, conducted based on OECD Performance Standard No. 356 by one lead laboratory and four participating laboratories, aimed to validate the relevance and reliability of the KeraSkin™ Phototoxicity Assay for regulatory application in the safety assessment of cosmetics and drugs. Based on the test results, the 12 reference chemicals showed 91.7% to 100% within-lab reproducibility and 100% between-lab reproducibility in all participating labs. Further, the predictive capacity for the 12 reference chemicals calculated based on the total number of runs (144) showed 100% sensitivity (72/72), 98.6% specificity (71/72), and 99.3% accuracy (143/144). Overall predictive capacity (32 test chemicals) calculated based on the total number of runs (164) showed 97.6% (80/82) sensitivity, 97.6% (80/82) specificity, and 97.6% (160/164) accuracy. KeraSkin™ Phototoxicity Assay thus fulfills the requirements to be included as a 'me-too' test method in OECD TG 498.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Validation of an Endopep-suspension immunoassay for the diagnostics of human botulism. 内肽类悬液免疫分析法诊断人肉毒杆菌中毒的验证。

ALTEX Pub Date : 2025-05-19 DOI: 10.14573/altex.2412181

Maximilian Steinberg, Laura-Varenne Wilk, Daniel Stern, Jasmin Weisemann, Ute Messelhäußer, Matthias Wittwer, Maren Krüger, Hans Werner Mages, Andreas Rummel, Martin B Dorner, Brigitte G Dorner

{"title":"Validation of an Endopep-suspension immunoassay for the diagnostics of human botulism.","authors":"Maximilian Steinberg, Laura-Varenne Wilk, Daniel Stern, Jasmin Weisemann, Ute Messelhäußer, Matthias Wittwer, Maren Krüger, Hans Werner Mages, Andreas Rummel, Martin B Dorner, Brigitte G Dorner","doi":"10.14573/altex.2412181","DOIUrl":"https://doi.org/10.14573/altex.2412181","url":null,"abstract":"Botulism is a potentially life-threatening disease caused by botulinum neurotoxin (BoNT)-producing bacteria of the genus Clostridium. Laboratory detection of BoNTs in patients' samples is essential to confirm clinical diagnoses and to identify the causative BoNT serotype. The current 'gold standard' method for BoNT detection is the mouse bioassay (MBA), a highly stressful animal experiment. A viable animal experiment replacement method must demonstrate high sensitivity, specificity, reproducibility and robustness, as well as comprehensive BoNT subtype detection, and be widely accepted in the field, necessitating rigorous validation. Here, we report on the validation of a previously established in vitro endopeptidase suspension immunoassay (Endopep-SIA) for the simultaneous detection, differentiation and quantification of BoNT serotypes A and B, the most frequent serotypes associated with human botulism. This assay uses monoclonal antibodies for BoNT extraction, followed by detection of the catalytic activity using neoepitope-specific monoclonal antibodies and suspension array technology. The Endopep-SIA showed high reproducibility with intra- and inter-assay variabilities between 7 and 22%, it demonstrated a sensitivity two- to twenty-fold higher than the MBA for BoNT in buffer samples and was equally sensitive for human serum samples with a limit of detection of 0.4 MLD/mL for BoNT/A and 1.0 MLD/mL for BoNT/B. Importantly, it reliably detected all six BoNT/A and six BoNT/B subtypes tested, including clinically relevant and bivalent strains, hereby proving high diagnostic safety. Based on the results obtained, we expect the Endopep-SIA to be instrumental in markedly reducing the number of animals used in botulism diagnostics.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Moving towards making (quantitative) structure-activity relationships ((Q)SARs) for toxicity-related endpoints findable, accessible, interoperable and reusable (FAIR). 朝着建立（定量的）结构-活性关系（(Q) sar）的方向发展，使毒性相关端点可找到、可访问、可互操作和可重用（FAIR）。

ALTEX Pub Date : 2025-05-19 DOI: 10.14573/altex.2411161

Samuel J Belfield, Homa Basiri, Swapnil Chavan, Georgios Chrysochoou, Steven J Enoch, James W Firman, Anish Gomatam, Barry Hardy, Palle S Helmke, Judith C Madden, Uko Maran, Eric March-Vila, Nikolai G Nikolov, Manuel Pastor, Geven Piir, Sulev Sild, Aljoša Smajić, Nicoleta Spînu, Eva B Wedebye, Mark T D Cronin

{"title":"Moving towards making (quantitative) structure-activity relationships ((Q)SARs) for toxicity-related endpoints findable, accessible, interoperable and reusable (FAIR).","authors":"Samuel J Belfield, Homa Basiri, Swapnil Chavan, Georgios Chrysochoou, Steven J Enoch, James W Firman, Anish Gomatam, Barry Hardy, Palle S Helmke, Judith C Madden, Uko Maran, Eric March-Vila, Nikolai G Nikolov, Manuel Pastor, Geven Piir, Sulev Sild, Aljoša Smajić, Nicoleta Spînu, Eva B Wedebye, Mark T D Cronin","doi":"10.14573/altex.2411161","DOIUrl":"https://doi.org/10.14573/altex.2411161","url":null,"abstract":"(Quantitative) structure-activity relationships ((Q)SARs) are widely used in chemical safety assessment to predict toxicological effects. Many thousands of (Q)SAR models have been developed and published, however, few are easily available to use. This investigation has applied previously developed Findability, Accessibility, Interoperability, and Reuse (FAIR) Principles for in silico models to six published, different, machine learning (ML) (Q)SARs for the same toxicity dataset (inhibition of growth to Tetrahymena pyriformis). The majority of principles were met, however, there are still gaps in making (Q)SARs FAIR. This study has enabled insights into, and recommendations for, the FAIRification of (Q)SARs including areas where more work and effort may be required. For instance, there is still a need for (Q)SARs to be associated with a unique identifier and full data / metadata for toxicological activity or endpoints, molecular properties and descriptors, as well as model description to be provided in a standardised manner. A number of solutions to the challenges were identified, such as building on the QSAR Model Reporting Format (QMRF) and the application of QSAR Assessment Framework (QAF). This study also demonstrated that resources such as the QSAR Databank (QsarDB, www.qsardb.org) are valuable in storing ML QSARs in a searchable database and also provide a Digital Object Identifier (DOI). Many activities related to FAIR are currently underway and (Q)SAR modellers should be encouraged to utilise these to move towards the easier access and use of models. Enabling FAIR computational toxicology models will support the overall progress towards animal free chemical safety assessment.","PeriodicalId":520550,"journal":{"name":"ALTEX","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0