Connecting high throughput assay results to animal test outcomes
Attendees at a Feb. 17-18 workshop identified specific actions needed to enable high throughput test data to begin serving existing toxicity testing needs.
The workshop, titled “In Vitro to In Vivo Extrapolation for High Throughput Prioritization and Decision Making” was co-organized by the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the U.S. Environmental Protection Agency (EPA). The event, which attracted nearly 100 attendees, was held at EPA in Research Triangle Park, North Carolina and included a poster session (see sidebar).
Predicting chemical effects in living systems
The goal of in vitro to in vivo extrapolation (IVIVE) is to use data from in vitro tests, which measure the effects of chemicals on cultured cells or biological molecules, to predict how exposure to those chemicals might cause illness or injury in animals or people. “[IVIVE is] the essential component missing between high throughput screening and the animal world,” said NICEATM Director Warren Casey, Ph.D., during his opening remarks.
Organizers of the event acknowledged that the lack of health data for thousands of chemicals currently in use is partly due to the time and expense of generating data using traditional animal tests. High throughput testing holds promise for addressing this data gap, but methods to connect high throughput and other in vitro test outcomes with toxicity in animals need to be more fully developed to achieve broad acceptance of this approach.
Short-term actions recommended
A key recommendation was the creation of a central database of IVIVE prediction models and the data used to build them, which would allow the models to be shared and tested. Such a database could also help standardize data formatting, model development methods, and terminology, which workshop participants agreed was a critical need.
Participants also stressed the need to better understand differences between chemicals and pharmaceuticals. IVIVE methods, which were originally developed to predict behavior of pharmaceuticals in living systems, may incorporate assumptions that cannot be applied to industrial chemicals.
A third recommendation was to use IVIVE to help select doses for tests that will still need to be conducted using animals. Using in vitro test results in this way could improve the quality and relevance of data from animal tests, potentially reducing animal use and avoiding highly toxic doses, both of which would improve animal welfare.
Attendees also identified broader concepts that still need discussion, including:
- Data-poor regulatory contexts in which in vitro test data could be useful.
- International acceptance of in vitro data as a substitute for animal tests when appropriate.
- The potential for IVIVE to predict chemical effects on sensitive populations, such as infants, children, the elderly, and people with specific diseases.
Presentation slides and other materials from the workshop are available on the NICEATM website. The workshop conclusions will be summarized in a paper to be submitted this year to a peer-reviewed journal.
(Catherine Sprankle is a communications specialist for ILS, the contractor supporting NICEATM.)