Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity
Anna Bal-Price,Helena T. Hogberg,Kevin M. Crofton,Mardas Daneshian,Rex E. FitzGerald,Ellen Fritsche,Tuula Heinonen,Susanne Hougaard Bennekou,Stefanie Klima,Aldert H. Piersma,Magdalini Sachana,Timothy J. Shafer,Andrea Terron,Florianne Monnet-Tschudi,Barbara Viviani,Tanja Waldmann,Remco H.S. Westerink,Martin F. Wilks,Hilda Witters,Marie-Gabrielle Zurich,Marcel Leist +20 more
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Suggestions are made on how DNT NAMs may be assembled into an integrated approach to testing and assessment (IATA), and a vision is presented on how further NAM development may be guided by knowledge of signaling pathways necessary for brain development, DNT pathophysiology, and relevant adverse outcome pathways (AOP).Abstract:
Multiple non-animal-based test methods have never been formally validated. In order to use such new approach methods (NAMs) in a regulatory context, criteria to define their readiness are necessary. The field of developmental neurotoxicity (DNT) testing is used to exemplify the application of readiness criteria. The costs and number of untested chemicals are overwhelming for in vivo DNT testing. Thus, there is a need for inexpensive, high-throughput NAMs, to obtain initial information on potential hazards, and to allow prioritization for further testing. A background on the regulatory and scientific status of DNT testing is provided showing different types of test readiness levels, depending on the intended use of data from NAMs. Readiness criteria, compiled during a stakeholder workshop, uniting scientists from academia, industry and regulatory authorities are presented. An important step beyond the listing of criteria, was the suggestion for a preliminary scoring scheme. On this basis a (semi)-quantitative analysis process was assembled on test readiness of 17 NAMs with respect to various uses (e.g. prioritization/screening, risk assessment). The scoring results suggest that several assays are currently at high readiness levels. Therefore, suggestions are made on how DNT NAMs may be assembled into an integrated approach to testing and assessment (IATA). In parallel, the testing state in these assays was compiled for more than 1000 compounds. Finally, a vision is presented on how further NAM development may be guided by knowledge of signaling pathways necessary for brain development, DNT pathophysiology, and relevant adverse outcome pathways (AOP).read more
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References
More filters
Journal ArticleDOI
Neurotoxic reactive astrocytes are induced by activated microglia
Shane A. Liddelow,Kevin A. Guttenplan,Laura E. Clarke,Frederick C. Bennett,Christopher J. Bohlen,Lucas Schirmer,Mariko L. Bennett,Alexandra E. Münch,Won-Suk Chung,Todd C. Peterson,Daniel K. Wilton,Arnaud Frouin,Brooke A. Napier,Nikhil Panicker,Manoj Kumar,Marion S. Buckwalter,David H. Rowitch,Valina L. Dawson,Ted M. Dawson,Beth Stevens,Ben A. Barres +20 more
TL;DR: It is shown that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A2 astroCytes, which are abundant in various human neurodegenerative diseases.
Journal ArticleDOI
The zebrafish reference genome sequence and its relationship to the human genome.
Kerstin Howe,Matthew D. Clark,Carlos Torroja,Carlos Torroja,James Torrance,Camille Berthelot,Matthieu Muffato,John E. Collins,Sean Humphray,Karen McLaren,Lucy Matthews,Stuart McLaren,Ian M Sealy,Mario Caccamo,Carol Churcher,Carol Scott,Jeffrey C. Barrett,Romke Koch,Gerd Jörg Rauch,Simon D. M. White,William Chow,Britt Kilian,Leonor T. Quintais,José Afonso Guerra-Assunção,Yi Zhou,Yong Gu,Jennifer Yen,Jan Hinnerk Vogel,Tina Eyre,Seth Redmond,Ruby Banerjee,Jianxiang Chi,Beiyuan Fu,Elizabeth Langley,Sean Maguire,Gavin K. Laird,D. M. Lloyd,Emma J. Kenyon,Sarah Donaldson,Harminder Sehra,Jeff Almeida-King,Jane E. Loveland,Stephen J. Trevanion,Matthew Jones,Michael A. Quail,Dave Willey,Adrienne Hunt,John Burton,Sarah Sims,Kirsten McLay,Bob Plumb,J. C. Davis,Chris Clee,Karen Oliver,Richard M. Clark,Clare Riddle,David Eliott,Glen Threadgold,Glenn Harden,Darren Ware,Beverly Mortimer,Giselle Kerry,Paul Heath,Benjamin Phillimore,Alan Tracey,N Corby,Matthew Dunn,Christopher M. Johnson,Jonathan Wood,Susan J. Clark,Sarah Pelan,Guy Griffiths,Michelle Smith,Rebecca Glithero,Philip Howden,Nick Barker,Christopher Stevens,Joanna Harley,Karen Holt,Georgios Panagiotidis,J Lovell,Helen Beasley,Carl Henderson,Daria Gordon,Katherine Auger,Debbie E. Wright,Joanna Collins,Claire Raisen,Lauren Dyer,Kenric Leung,Lauren Robertson,Kirsty Ambridge,Daniel Leongamornlert,Sarah McGuire,Ruth Gilderthorp,C Griffiths,Deepa Manthravadi,Sarah Nichol,Gary L A Barker,S. Whitehead,Michael Kay,Jacqueline Brown,Clare Murnane,Emma Gray,Matthew Humphries,N Sycamore,Darren Barker,David S. Saunders,J. M. Wallis,A K Babbage,S Hammond,M Mashreghi-Mohammadi,Lucy Barr,Sancha Martin,Paul Wray,Andrew D. Ellington,Nicholas Matthews,Matthew Ellwood,Rebecca Woodmansey,Graham Clark,James D. Cooper,A Tromans,Darren Grafham,C. D. Skuce,Richard Pandian,Robert Andrews,Elliot Harrison,A M Kimberley,J Garnett,Nigel Fosker,Rebekah Hall,P Garner,Daniel P. Kelly,Christine P. Bird,Sophie Palmer,Ines Gehring,Andrea Berger,Christopher M. Dooley,Christopher M. Dooley,Zübeyde Ersan-Ürün,Cigdem Eser,Horst Geiger,Maria Geisler,Lena Karotki,Anette Kirn,Judith Konantz,Martina Konantz,Martina Oberländer,Silke Rudolph-Geiger,Mathias Teucke,Kazutoyo Osoegawa,Baoli Zhu,Amanda Rapp,Sara Widaa,Cordelia Langford,Fengtang Yang,Nigel P. Carter,Jennifer Harrow,Zemin Ning,Javier Herrero,Steve Searle,Anton J. Enright,Robert Geisler,Robert Geisler,Ronald H.A. Plasterk,Charles Lee,Monte Westerfield,Pieter J. de Jong,Leonard I. Zon,John H. Postlethwait,Christiane Nüsslein-Volhard,Tim Hubbard,Hugues Roest Crollius,Jane Rogers,Derek L. Stemple +174 more
TL;DR: A high-quality sequence assembly of the zebrafish genome is generated, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map, providing a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebra fish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
Journal ArticleDOI
Trk receptors: roles in neuronal signal transduction.
Eric J. Huang,Louis F. Reichardt +1 more
TL;DR: The most fascinating aspect of Trk receptor-mediated signaling is its interplay with signaling promoted by the pan-neurotrophin receptor p75NTR, which activates a distinct set of signaling pathways within cells that are in some instances synergistic and in other instances antagonistic to those activated by Trk receptors.
Journal ArticleDOI
Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child.
James E. Haddow,Glenn E. Palomaki,Walter C. Allan,Josephine Williams,George J. Knight,June Gagnon,Cheryl E. O’heir,Marvin L. Mitchell,Rosalie J. Hermos,Susan E. Waisbren,James D. Faix,Robert Z. Klein +11 more
TL;DR: Undiagnosed hypothyroidism in pregnant women may adversely affect their fetuses; therefore, screening for thyroid deficiency during pregnancy may be warranted.
Journal ArticleDOI
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