stoptox an in silico alternative to animal testing for acute systemic and topical toxicity

• DOI: 10.17615/brxt-n696
• Publication Date: 2020-11-25
• Authors: Joyce V.B. Borba; Vinicius M. Alves; Rodolpho C. Braga; Daniel R. Korn; Kirsten Overdahl; Arthur C. Silva; Steven U.S. Hall; Erik Overdahl; Nicole Kleinstreuer; Judy Strickland; David Allen; Carolina Horta An...; Eugene N. Muratov; Alexander Tropsha
• Keywords: 0303 health sciences; 03 medical and health sciences; Pharmaceutical Preparations; Research; Animals; Quantitative Structure-Activity Relationship; Computer Simulation; Cosmetics; Pesticides; Animal Testing Alternatives; Hazardous Substances; 3. Good health

Since 2009, animal testing for cosmetic products has been prohibited in Europe, and in 2016, US EPA announced their intent to modernize the so-called "6-pack" of acute toxicity tests (acute oral toxicity, acute dermal toxicity, acute inhalation toxicity, skin irritation and corrosion, eye irritation and corrosion, and skin sensitization) and expand acceptance of alternative methods to reduce animal testing of pesticides. We have compiled, curated, and integrated the largest publicly available dataset and developed an ensemble of QSAR models for all six endpoints. All models were validated according to the OECD QSAR principles and tested using newly identified data on compounds not included in the training sets. We have established a publicly accessible Systemic and Topical chemical Toxicity (STopTox) web portal (https://stoptox.mml.unc.edu/) integrating all developed models for “6-pack” assays. This portal can be used by scientists and regulators to identify putative toxicants or non-toxicants in chemical libraries of interest.