Each day we are bathed in thousands of man-made chemicals that never existed in nature. They are in cosmetics and shampoo, food packaging and plastic containers, clothing and building materials, furniture and electronic devices.
Although the U.S. now produces more than 500 million tons of synthetic chemicals annually, a major 鈥渢oxicological information gap鈥� has developed regarding the risks they pose to human health and the environment. According to a number of government reports, less than 10 percent of the 80,000-odd chemicals in general commerce have been tested adequately to determine their health risks.
The has announced the establishment of three new centers to develop alternative approaches for toxicity testing that could help fill the troubling gap. One is the , which will receive $6 million for four years to develop toxicity test procedures based on three-dimensional human cell cultures, rather than the combination of standard two-dimensional cell cultures and whole animal testing that has been de rigeur until now.
VPROMPT is a collaboration between investigators at Vanderbilt University and the University of Pittsburgh. The lead principal investigator is , associate professor of physics at Vanderbilt. The five co-principal investigators are Research Associate Professor , Professor , director of the Women鈥檚 Reproductive Health Research Center, and Gordon A. Cain University Professor at Vanderbilt and , director of the Center for Cellular and Molecular Engineering, and , director of the Drug Discovery Institute, at Pittsburgh.
鈥淸lquote]Given the situation we face, traditional toxicology testing procedures are simply inadequate[/lquote],鈥� said Hutson. 鈥淎 full toxicological evaluation for a single chemical using traditional methods can cost millions of dollars, involve hundreds of test animals and take years to complete. And, as if the time and cost weren鈥檛 bad enough, existing tests haven鈥檛 proven very good at predicting chemicals鈥� effects on humans.鈥�
The primary goal of the new center is to develop a series of 3-D human cell cultures that are heavily wired up with different sensors to record how they respond when exposed to small concentrations of potentially toxic chemicals. The forefront of cell biology is moving away from traditional 2-D culture of a single cell type towards 3-D cell culture of multiple cell types that more closely mimic the microenvironment of particular organs. These more complex cultures exhibit cell behaviors that are much more like those seen by cells in living animals. By making sure the cultures use human cells, the researchers hope to avoid misleading toxicity results caused by differences in how animal and human cells respond to the same chemical.
鈥淲e are very excited about the new Vanderbilt/Pittsburgh partnership to develop and apply innovative tissue-on-a-chip technologies to identify and evaluate potential harmful agents in the environment, and contribute towards improving the nation鈥檚 health,鈥� said Tuan.
The researchers will develop four test platforms: one using liver cells; one using fetal membrane cells; one using mammary gland cells; and one using cells involved in limb and joint growth. They selected the liver because one of its functions is to remove toxic substances from blood coming from the digestive system before they can spread throughout the body. The fetal membrane and mammary gland cells were included because of the roles they play in reproduction. And they choose the cells involved in limb and joint growth because their role in development.
The researchers will expose the 3-D cultures to a battery of previously identified toxic chemicals that have been extensively studied using traditional methods so they can compare the results and determine how well the procedures they have developed predict the results of the older tests.