Dataset Information

Genetic toxicology in silico protocol.

ABSTRACT: 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.

SUBMITTER: Hasselgren C

PROVIDER: S-EPMC7485926 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic toxicology in silico protocol.

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

Regulatory toxicology and pharmacology : RTP 20190611

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 ...[more]

PMID: 31195068

Similar Datasets

Project description:To ascertain attitudes to resourcing, collaboration and publication in toxicology, a survey was developed and distributed to British Toxicology Society (BTS) members. The survey comprised 14 questions with 5 response options (strongly agree; agree; conflicted; disagree; strongly disagree) and a free text box. One hundred completed surveys were received by the cut-off date for data analysis. Unsurprisingly, 60% of participants disagreed or strongly disagreed that toxicology research is adequately funded in the UK; only 12% agreed with this statement. A similar proportion of participants (53%) disagreed with the statement that funding councils give equal opportunity to toxicology whereas 31% were conflicted on this point. An overwhelming 97% of respondents agreed that collaboration is important in driving toxicology research whereas only 38% agreed that competition is important. When this question was broadened out beyond the discipline of toxicology, a similar profile was seen suggesting that participants held similar views on toxicology versus other types of research. Many respondents were conflicted regarding the role of competition both in toxicology and in other research disciplines. Free text comments suggested that some competition is good to drive quality but can be counterproductive when competing for limited resources. Most participants were in favour of making toxicology research data openly available (86%) and in favour of open access publication (89%) although there were reservations about the cost of open access. Many (60%) thought the current system of peer review is fair but 65% also supported the idea of double-blind peer review (where both reviewer and author are anonymized). Others suggested a step in the opposite direction towards increased transparency (revealing and holding reviewers to account) would be preferable. Overall, there was a broad theme in free text responses that the need for experienced toxicologists has increased at a time when training and investment in the discipline has declined. However, not all respondents held that view with some noting that toxicology both as a research and as an applied discipline is strong within the UK scientific community.

Dataset Information

Genetic toxicology in silico protocol.

Publications

Genetic toxicology in silico protocol.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets