ILSI Research Foundation
Workshop: Evaluating the Human Relevance of Modes of Action in Animals
This full-day workshop presents a systematic approach to characterizing the
mode(s) of action (MOA) of toxicants and will give participants “hands-on” experience in the application of a framework for evaluating the relevance of an animal mode of action in assessing human risk. Frameworks for characterizing MOA data for carcinogens and analyzing its human relevance have been developed over the past decade and cited in various national and international risk assessment guidelines. More recently, these concepts have been extended to non-cancer endpoints including reproductive, developmental, neurologic and other toxic effects.
The workshop will demonstrate the use of an MOA human relevance framework, through a combination of lecture and interactive case studies with group participation. An opening tutorial will introduce workshop participants to basic concepts and walk them through a model case study. This leads into a series of facilitated interactive case studies in which participants analyze a diverse series of examples of varying complexity, drawn from recent peer reviewed publications involving “real world” chemicals. Case studies will examine issues such as the incorporation of kinetic and dynamic information and its impact on cross-species extrapolation, the use of precursor data in dose-response analysis, and sufficiency of evidence for establishing an MOA and its human relevance. The cases selected illustrate the comparability between MOA analysis for cancer and non-cancer endpoints, the problem of data-poor situations that preclude a full MOA human relevance analysis, and differences in animal-human MOA analysis based on differences in developmental stage.
Participants are provided with background materials, copies of the presentations, and other materials specially developed for the case studies. Case studies are worked through in small breakout groups, each guided by a speaker/facilitator. The five speaker/facilitators for this workshop – Dr. Kevin Crofton, Dr. Vicki Dellarco, Dr. Penny Fenner-Crisp, Ms. Bette Meek, and Dr. Jennifer Seed - have been leaders in the development of MOA human relevance analysis and have extensive experience in its practical use.
This workshop also will feature opening remarks by Dr. George Gray, EPA Assistant Administrator for Research and Development, speaking on “Advancing Risk Assessment at EPA.” This presentation and the opening workshop tutorials are open to the public at no charge; the remainder of the workshop, including the interactive case studies, is limited to workshop registrants. The workshop will conclude with a Plenary Lecture given by Dr. James Swenberg, UNC Chapel Hill titled “Key Events for a Mutagenic MOA: Implications for Risk Assessment”.