Genetic toxicology in silico protocol

Publikation: Beiträge in ZeitschriftenZeitschriftenaufsätzeForschungbegutachtet


  • Catrin Hasselgren
  • Ernst Ahlberg
  • Yumi Akahori
  • Alexander Amberg
  • Lennart T. Anger
  • Franck Atienzar
  • Scott Auerbach
  • Lisa Beilke
  • Phillip Bellion
  • Romualdo Benigni
  • Joel Bercu
  • Ewan D. Booth
  • Dave Bower
  • Alessandro Brigo
  • Zoryana Cammerer
  • Mark T.D. Cronin
  • Ian Crooks
  • Kevin P. Cross
  • Laura Custer
  • Krista Dobo
  • Tatyana Doktorova
  • David Faulkner
  • Kevin A. Ford
  • Marie C. Fortin
  • Markus Frericks
  • Samantha E. Gad-McDonald
  • Nichola Gellatly
  • Helga Gerets
  • Véronique Gervais
  • Susanne Glowienke
  • Jacky Van Gompel
  • James S. Harvey
  • Jedd Hillegass
  • Masamitsu Honma
  • Jui Hua Hsieh
  • Chia Wen Hsu
  • Tara S. Barton-Maclaren
  • Candice Johnson
  • Robert Jolly
  • David Jones
  • Ray Kemper
  • Michelle O. Kenyon
  • Naomi L. Kruhlak
  • Sunil A. Kulkarni
  • Penny Leavitt
  • Scott Masten
  • Scott Miller
  • Chandrika Moudgal
  • Wolfgang Muster
  • Alexandre Paulino
  • Elena Lo Piparo
  • Mark Powley
  • Donald P. Quigley
  • M. Vijayaray Reddy
  • Andrea Nicole Richarz
  • Benoit Schilter
  • Ronald D. Snyder
  • Lidiya Stavitskaya
  • Reinhard Stidl
  • David T. Szabo
  • Andrew Teasdale
  • Raymond R. Tice
  • Alejandra Trejo-Martin
  • Anna Vuorinen
  • Brian A. Wall
  • Pete Watts
  • Angela T. White
  • Joerg Wichard
  • Kristine L. Witt
  • Adam Woolley
  • David Woolley
  • Craig Zwickl
  • Glenn J. Myatt

In silico toxicology (IST) approaches to rapidly assess chemical hazard, and usage of such methods is increasing in all applications but especially for regulatory submissions, such as for assessing chemicals under REACH as well as the ICH M7 guideline for drug impurities. There are a number of obstacles to performing an IST assessment, including uncertainty in how such an assessment and associated expert review should be performed or what is fit for purpose, as well as a lack of confidence that the results will be accepted by colleagues, collaborators and regulatory authorities. To address this, a project to develop a series of IST protocols for different hazard endpoints has been initiated and this paper describes the genetic toxicity in silico (GIST) protocol. The protocol outlines a hazard assessment framework including key effects/mechanisms and their relationships to endpoints such as gene mutation and clastogenicity. IST models and data are reviewed that support the assessment of these effects/mechanisms along with defined approaches for combining the information and evaluating the confidence in the assessment. This protocol has been developed through a consortium of toxicologists, computational scientists, and regulatory scientists across several industries to support the implementation and acceptance of in silico approaches.

ZeitschriftRegulatory Toxicology and Pharmacology
Anzahl der Seiten21
PublikationsstatusErschienen - 01.10.2019

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