The RISK-HUNT3R project presented a case study at the EPAA Designathon – New approach methodologies workshop, which was held on the 20th-22nd of March 2024 at the JRC in ISPRA, Italy.

The workshop discussed case studies which proposed a Next Generation Hazard Assessment framework based on NAMs to classify compounds as high, moderate or low toxic with regard to systemic toxicity in humans. Conceptually, toxicodynamic and kinetic properties contribute to this classification. All case studies were asked to assess one to many of 150 preselected model compounds. Beside RHT3R also Ontox and PrecisionTox, also being part of the ASPIS cluster contributed case studies.

RH3R team attending the 2024 EPAA Designathon Workshop.

RHT3R Case Study 2 team presented an integrated approach, which applied high throughput NAM data from ToxCast inventory, the disease associations from the Chemical Effect Predictor as well as high throughput PBK modeling. RHT3R first developed these three models and determined their predictivity with regard to STOT-RE predictions by using about 66 case study compounds from case study 2. Then they performing approach was applied to nine Designathon compounds to predict there STOT-RE classification.

The workshop used the different case studies as starting point to discuss the main principles of NAM based toxicokinetic and dynamic assessment. Discussion of shared assessment elements and main differences helped to crystallize out that it would be a good idea to assess different endpoints by using different criteria and testing approaches, e.g. for acute toxicity, CMR or STOT-RE. While the assumptions and approaches in high throughput kinetic assessments were already fairly similar, more work is needed to agree on the testing strategy for toxicodynamic properties. Workshops like this a needed to evaluate a variety of ideas to then include new ideas into future developments.

RISK-HUNT3R will continue the work in case study 2 using other relevant and promising high throughput methods e.g. expanding to cell painting and reporter based assays. A subset of the Designathon compounds will be used as external validation set.

All information regarding the EPAA Designathon workshop are available here. Recording of the EPAA DESIGNATHON workshop is available here on the European Commission website and a flash report of the event here.