Harnessing In Silico, In Vitro, and In Vivo Data to Understand the Toxicity Landscape of Polycyclic Aromatic...

Area of Science:

• Environmental Chemistry
• Toxicology
• Computational Chemistry

Background:

• Polycyclic aromatic compounds (PACs) are widespread environmental contaminants from incomplete combustion.
• Carcinogenicity is a primary health concern, but other toxicities exist.
• Research has focused mainly on polycyclic aromatic hydrocarbons (PAHs), neglecting other PACs.

Purpose of the Study:

• To develop a data-driven strategy for hazard characterization of PACs.
• To prioritize PACs for further toxicological testing and chemical read-across.
• To leverage diverse data streams for a comprehensive understanding of PAC toxicity.

Main Methods:

• Clustering PACs based on in silico toxicity profiles across 8 categories.
• Integrating in silico toxicity, in vitro activity, and structural fingerprints.
• Analyzing in vivo data availability for PACs.

Main Results:

• PACs with similar substituted groups or heterocyclic structures showed similar toxicity profiles, indicating suitability for read-across.
• Genotoxicity/carcinogenicity and xenobiotic homeostasis/stress response were dominant factors in toxicity variation.
• Identified data-poor (e.g., hydroxylated-PAHs) and data-rich (e.g., parent PAHs) regions for targeted in vivo assessment.

Conclusions:

• A data-driven approach effectively categorizes PACs for toxicity assessment.
• Structural similarities can predict toxicity, guiding read-across strategies.
• Prioritization of PACs for further testing is crucial for public health protection.