Superfund Research Program
Systems Approach to Define Toxicity of Complex PAH Mixtures
Project Leader: Robyn L. Tanguay
Grant Number: P42ES016465
Funding Period: 2009-2019
The developmental toxicity of hundreds of polycyclic aromatic hydrocarbons (PAHs) have been assessed in the zebrafish model. A rapid, sensitive and cost-effective zebrafish model was developed to assess the toxicology of particulate air pollution. This provides a path to identify the toxic material(s) in air pollution samples, and to discover how these toxic chemicals cause disease. In collaboration with Kim Anderson, the research group demonstrated passive sampling and the zebrafish systems are powerful partners to evaluate real world chemical mixtures. The research group constructed a PAH mixture with the top 10 most prevalent PAHs (SM10) from a Superfund site. Using zebrafish, they measured the uptake of these PAHs and evaluated the developmental and neurotoxicity of SM10 and the 10 individual PAHS. It was found that the SM10 and only three of the individual PAHs were toxic. In addition, it was found that the toxicity of a mixture of the three toxic chemicals (SM3) was similar to SM10. The results demonstrated that the overall toxicity in the mixtures could be explained by simple addition. Collectively, these results exemplify the utility of zebrafish to investigate the developmental and neurotoxicity of complex mixtures. Additionally, this year the research group identified a long noncoding RNA, sox9b long intergenic noncoding RNA (slincR), which undergoes increased expression by multiple PAHs. SlincR is recruited to the sox9b 5' UTR to repress transcription, it regulates cartilage development, and has a role in produce hemorrhaging. The research group identified slincR orthologues in humans, thus these findings have important implications for understanding PAH toxicity in humans.