Exploring In Vitro/In Vivo Correlation: Lessons Learned from Analyzing Phase I Results of the US EPA's ToxCast Project

Abstract

The research on alternative toxicological methods provides, among other things, a privileged viewpoint on one of the central issues of modern biomedical research—the relationship between (a) biological phenomena observed at the level of tissues and organisms and (b) their cellular and molecular bases as studied in isolated systems in vitro. The newly released ToxCast Phase 1 results, subject to initial analysis, converge with evidence from other fields (e.g., research on drug design with intensive use of omics technologies, traditional research on alternative tests) in indicating a low degree of the in vitro/in vivo correlation overall. In addition, this and other approaches point to the need for combining biological and chemical information in exploring the in vitro to in vivo connection.

Keywords:

• alternative testing
• three Rs
• toxicity
• reductionism
• systems biology
• ToxCast

ACKNOWLEDGEMENTS

The continued interest and open, cooperative attitude of Ann M. Richard is gratefully acknowledged. This work was partially supported by the following projects: Project EU FP6 no. 037017 OSIRIS “Optimized Strategies for Risk Assessment of Industrial Chemicals through Integration of Non-Test and Test Information”; and Project EU FP7 no. 200787 OpenTox “An Open Source Predictive Toxicology Framework.”