Abstracts from the In Vitro Toxicology Society Annual Meeting Radisson Blu Hotel Glasgow, United Kingdom November 14–15, 2016
approaches in toxicology cover many aspects of compiling and curating information and deriving knowledge and models from it. With regard to organ level toxicity, there is a trend to move away from models for apical endpoints to identifying features of molecules associated with specific effects. Collections of Structure-Activity Relationships (SARs), often described as “structural alerts”, have been available for many years for certain toxicities. Recently there has been a shift away from the capture of knowledge from expert toxicologists regarding toxicological outcomes, to defining structural alerts for “Molecular Initiating Events” (MIEs). This has allowed for, approaches to be better aligned with mechanistic understanding, with the advent and promotion of Adverse Outcome Pathways (AOPs) providing guidance and inspiration. Recent advances include the development of, Peter C. Rubenwolf, for DNA and protein binding) as well as using novel sources of information, knowledge, derived from the ChEMBL database, of binding to nuclear receptors relevant to liver toxicity. The better understanding of MIEs allows for improvements to grouping and read-across. The challenges for the, prediction of organ level effects include ensuring adequate coverage of the domains of the profilers and making extrapolations from, (and, ) results to relevant, exposures. · Applied In Vitro Toxicology · 2016
In silico approaches in toxicology cover many aspects of compiling and curating information and deriving knowledge and models from it.With regard to organ level toxicity, there is a trend to move away from models for apical endpoints to identifying features of molecules associated with specific effects.Collections of Structure-Activity Relationships (SARs), often described as ''structural alerts'', have been available for many years for certain toxicities.Recently there has been a shift away from the capture of knowledge from expert toxicologists regarding toxicological outcomes, to defining structural alerts for ''Molecular Initiating Events'' (MIEs).This has allowed for in silico approaches to be better aligned with mechanistic understanding, with the advent and promotion of Adverse Outcome Pathways (AOPs) providing guidance and inspiration.Recent advances include the development of in silico profilers based on organic reaction chemistry (e.g. for DNA and protein binding) as well as using novel sources of information, e.g., knowledge, derived from the ChEMBL database, of binding to nuclear receptors relevant to liver toxicity.The better understanding of MIEs allows for improvements to grouping and read-across.The challenges for the in silico prediction of organ level effects include ensuring adequate coverage of the domains of the profilers and making extrapolations from in silico (and in vitro) results to relevant in vivo exposures.