Principles and procedures for assessment of acute toxicity incorporating in silico methods

The present IST protocol centers on in silico-based evidence as applied to support evaluation of acute toxicity. Given the diverse areas of application, scenarios and purposes for assessing acute toxicity (i.e., questions needing to be addressed for-cause), the intent of the protocol is to provide a generally applicable conceptual framework and not guidance for satisfying regulatory submission requirements. To develop this framework, emphasis is given to application of in silico methods supporting weight-of-evidence approaches, such as those commonly used in hazard identification and classification. The same principles, which are aimed toward assessing the level of confidence in an evaluation by improving transparency with respect to in silico model development, testing and performance, for communicating data relevance and reliability, and for exploring limitations of an approach, are expected to equally apply in other arenas. For scenarios requiring a formal writeup (e.g., when the assessment is part of a submission to a regulatory authority), a clear understanding of the purpose and objectives for making the assessment lays the groundwork for presenting material in a rational, well organized, and persuasive fashion, all of which help to facilitate the review process. Considerations for reporting are included following the discussion on relevance, reliability and confidence.

ZWICKL Craig;  GRAHAM Jessica C.;  JOLLY Robert A.;  BASSAN Arianna;  AHLBERG Ernst;  AMBERG Alexander;  ANGER Lennart T;  BEILKE Lisa D.;  BELLION Phillip;  BRIGO Alessandro;  BURLEIGH-FLAYER Heather;  CRONIN Mark T.D.;  DEVLIN Amy A.;  FISH Trevor;  GLOWIENKE Susanne;  GROMEK Kamila;  KARMAUS Agnes L.;  KEMPER Ray;  KULKARNI Sunil A;  LO PIPARO Elena;  MADIA Federica Anna Carla;  MARTIN Matthew;  MASUDA-HERRERA Melisa;  MCATEE Britt L.;  MESTRES Jordi;  MILCHAK Lawrence;  MOUDGAL Chandrika;  MUMTAZ Moiz;  MUSTER Wolfgang;  NEILSON Louise;  PATLEWICZ Grace;  PAULINO Alexandre;  RONCAGLIONI Alessandra;  RUIZ Patricia;  SZABO David T;  VALENTIN Jean-Pierre;  VARDAKOU Joanna;  WOOLLEY David;  MYATT Glenn J.; 

2023-01-27

ELSEVIER BV

JRC128586

2468-1113 (print),   

https://www.sciencedirect.com/science/article/pii/S2468111322000251?via%3Dihub,    https://publications.jrc.ec.europa.eu/repository/handle/JRC128586,   

10.1016/j.comtox.2022.100237 (online),