Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization

Area of Science:

• Environmental Chemistry
• Toxicology
• Risk Assessment

Background:

• Current component-based methods for polycyclic aromatic hydrocarbons (PAHs) mixture safety assessment have limitations.
• There is a need for established frameworks for utilizing sufficiently similar mixtures in safety evaluations.
• Polycyclic aromatic hydrocarbons (PAHs) are prevalent environmental contaminants requiring robust assessment strategies.

Purpose of the Study:

• To explore and establish frameworks for creating sufficiently similar mixtures for safety assessment.
• To compare different approaches for forming these similar mixtures.
• To identify the most effective method for prioritizing chemicals in mixture formation for hazard assessment.

Main Methods:

• Analyzed air samples for unsubstituted and alkylated PAHs.
• Created a synthetic Creosote-Fire Mix and identified hazardous components using toxicity and concentration data.
• Formed three types of sufficiently similar mixtures: based on relative abundance, toxicity values, and a combination approach.
• Performed hazard characterization using high-throughput screening in human bronchial epithelium and zebrafish models.

Main Results:

• Significant differences in chemical composition and potency were observed among the mixture formation approaches.
• The toxicity-based mixture (Tox Mix) demonstrated the highest potency in both human and zebrafish models.
• The combination approach (Weighted-Tox Mix) effectively prioritized chemicals with high exposure and hazard potential.

Conclusions:

• The combination approach (Weighted-Tox Mix) is ideal for mixture safety assessment, balancing chemical exposure and hazard.
• High-throughput screening in relevant models can effectively characterize the hazard of complex PAH mixtures.
• This study provides a framework for developing sufficiently similar mixtures for improved environmental mixture safety assessment.