In silico approaches in organ toxicity hazard assessment: Current status and future needs for predicting heart,...

Area of Science:

• Toxicology
• Computational Biology
• Pharmacology

Background:

• Kidneys, heart, and lungs are critical organ systems assessed for toxicity.
• Adverse effects are currently evaluated through traditional toxicity assessments.
• Emerging *in vitro* and *in silico* methods offer predictive capabilities.

Purpose of the Study:

• To review the current state of art in predicting organ toxicities using *in vitro* and *in silico* methods.
• To outline biological basis, processes, and endpoints for kidney, pulmonary, and cardiac toxicities.
• To describe current experimental and *in silico* approaches and their limitations.

Main Methods:

• Review of current literature on *in vitro* and *in silico* toxicity prediction.
• Analysis of biological basis, processes, and endpoints for organ toxicities.
• Examination of experimental approaches including secondary pharmacology panels.
• Description of *in silico* prediction methods and associated obstacles.

Main Results:

• Detailed review of kidney, pulmonary, and cardiac toxicity assessment methodologies.
• Identification of current experimental and *in silico* approaches for toxicity prediction.
• Elucidation of obstacles hindering the widespread use of *in silico* methods.

Conclusions:

• A standardized protocol for organ toxicity assessment would be valuable for regulatory and industrial applications.
• Widespread deployment of predictive methods is impeded by lack of mechanistic understanding, limited *in vitro* data, and insufficient *in vivo* databases.
• Further development is needed in incorporating ADME, safe dose prediction models, and a framework for toxicant characteristics.