Domenico Gadaleta

TL;DR: The history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods.

TL;DR: A number of approaches used to build the Applicability Domain are surveyed, focusing on strategies based on: a) physico-chemical, b) structural and c) response domains, which represents the chemical space from which a model is derived and where a prediction is considered to be reliable.

TL;DR: Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity.

TL;DR: (Quantitative) structure–activity relationships [(Q)SAR] proved a valid alternative to reduce and assist in vivo assays for assessing acute toxicological hazard and confirmed the relevance of developed models in regulatory frameworks, and the effectiveness of integrated modeling.

TL;DR: Toxicological endpoints and areas where further development is needed are discussed to provide an enlightened appraisal of this attractive new opportunity in REACH.