Grantee Research Project Results
Oral toxicity assessment of PAH mixtures using an in vitro 3D cell culture bioreactor mimicking the in vivo intestinal tract environment
EPA Grant Number: R840457Title: Oral toxicity assessment of PAH mixtures using an in vitro 3D cell culture bioreactor mimicking the in vivo intestinal tract environment
Investigators: Rodrigues, Debora , Liu, Xinli
Institution: University of Houston
EPA Project Officer: Aja, Hayley
Project Period: September 1, 2022 through May 1, 2025
Project Amount: $749,926
RFA: Development of Innovative Approaches to Assess the Toxicity of Chemical Mixtures Request for Applications (RFA) (2022) RFA Text | Recipients Lists
Research Category: CSS , Chemical Safety for Sustainability , Computational Toxicology , Endocrine Disruptors , Health Effects , Human Health , Mixtures , New Approach Methods (NAMs) , Safer Chemicals
Description:
Polycyclic aromatic hydrocarbons (PAHs) ubiquitous presence in the environment is a severe public health concern as many of them are known to be carcinogenic to humans. PAHs can enter the human body either through inhalation or consumption of contaminated food. The latter represents the most common mechanism of PAHs intake (2-500 ng/day) but has not received much attention. Current approaches to understanding the toxicology of environmental contaminants usually require in vivo experimentations with different animals. Still, they do not necessarily translate to actual human responses, can be expensive, laborious, and is of low throughput, especially for a large class of toxicants such as PAHs. To address this limitation, the objective of this study is to design and engineer an in vitro 3-Dimensional (3D) cell culture integrated into a flow-cell bioreactor to conduct the toxicological assessment of environmental PAH mixtures that can be found in food.
Objective:
This project hypothesizes that incorporating 3D cell culturing techniques in a bioreactor with a controlled temperature, growth conditions, and flow of nutrient media will induce growth and alter cell behavior like an in vivo intestinal tract environment, providing an efficient and realistic model to understand PAH mixtures health risk.
Approach:
This projecct involves using human, mice, and pig intestinal cells (since both have high genomic similarity to humans) to be cultured inside the 3D bioreactor to analyze toxicological markers and pathways of PAH mixtures. Additionally, we will evaluate human, pig, and mice gut microbiome ability to biodegrade PAHs compounds and whether the biodegradation byproducts can cause toxic effects to the intestinal tract. For validation, this novel 3D approach will be compared to an in vivo animal model (i.e., mice).
Expected Results:
Researchers expect that the in vitro and in vivo results will be similar for the mice model, which will validate the newly proposed method with the 3D system. Furthermore, the results will identify toxicological markers and pathways of PAH mixtures in humans.
Supplemental Keywords:
Risk assessment, PAH mixture, carcinogen, exposure, flow cell bioreactorProgress and Final Reports:
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.