A recent review out of the Oregon State University Superfund Research Program (OSU SRP) describes how zebrafish have become an important model to screen for chemical toxicity. The article, published in the journal Green Chemistry, points to major advances in testing methods that have positioned zebrafish as an applicable model for chemical safety evaluations and efforts to develop more sustainable chemicals.
According to the authors, led by OSU SRP Center investigator Robert Tanguay, Ph.D., there is a growing recognition that the use of traditional test models and empirical approaches is impractical to screen the toxicity of thousands of chemicals in the environment and hundreds of new chemicals introduced each year. This has prompted efforts to implement more predictive approaches to evaluate chemical toxicity early in product development.
The use of zebrafish has accelerated recently in genetic toxicology, high throughput screening (HTS), and behavioral testing. HTS technologies with zebrafish enable the screening of large chemical libraries for bioactivity early in the development of new chemicals. Previous research has shown that many toxic responses are shared among fish and mammals owing to their generally well-conserved development, cellular networks, and organ systems. These shared responses have been observed for chemicals that impair endocrine functioning, development, and reproduction, as well as those that elicit cardiotoxicity and carcinogenicity, among other diseases.
With zebrafish, researchers are able to characterize toxic effects of chemicals in a variety of cellular processes and compare those processes to changes in the fish, such as developmental malformations. Zebrafish also can be used to assess the toxicity of real-world multi-chemical exposures.
Tanguay leads an OSU SRP Center project that uses systems approaches in zebrafish to understand the mechanisms of toxicity of complex mixtures of polycyclic aromatic hydrocarbons (PAHs), which are routinely found at Superfund sites. Several studies have shown increased incidence of lung, skin, and urinary cancer in humans exposed to PAH mixtures. Many individual PAH compounds also have been classified as probable or possible carcinogens. Because PAHs are widespread in the environment as mixtures, it is difficult to tease out exposure and toxic effects. Researchers led by Tanguay are using zebrafish to identify environmentally relevant PAH mixtures that pose a hazard and to identify the gene responses that drive the toxic endpoints.