Comparative developmental toxicity of environmentally relevant oxygenated PAHs

Area of Science:

• Environmental Chemistry
• Toxicology
• Developmental Biology

Background:

• Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are ubiquitous environmental contaminants formed from combustion and PAH photo-oxidation.
• The human health risks associated with OPAHs remain largely uncharacterized.
• Developing zebrafish offer a sensitive model for assessing the developmental toxicity of environmental pollutants.

Purpose of the Study:

• To evaluate the developmental toxicity of 38 structurally diverse OPAHs using zebrafish.
• To identify structure-activity relationships governing OPAH toxicity.
• To elucidate the mechanisms of OPAH-induced toxicity, focusing on oxidative stress and mitochondrial function.

Main Methods:

• Zebrafish embryos were exposed to a dilution series of 38 OPAHs from 6 to 120 hours post-fertilization.
• Developmental endpoints, aryl hydrocarbon receptor (AHR) activation (CYP1A IHC), gene expression (qRT-PCR), and mitochondrial function (bioenergetics) were assessed.
• Hierarchical clustering was employed to analyze structure-activity relationships.

Main Results:

• Specific OPAH structures, including those with adjacent diones on 6-carbon moieties or terminal para-diones on multi-ring structures, were identified as most toxic.
• Exposure to certain OPAHs (e.g., 9,10-PHEQ, BEZO, 7,12-B[a]AQ, XAN) induced oxidative stress genes and decreased mitochondrial respiration (OCR).
• OPAH toxicity exhibited differential AHR dependency and was strongly linked to oxidative stress.

Conclusions:

• The study provides a comprehensive in vivo characterization of OPAH developmental toxicity in zebrafish.
• Structure-activity relationships highlight specific chemical features associated with high toxicity.
• Oxidative stress and mitochondrial dysfunction are key mechanisms underlying OPAH-induced developmental toxicity.