Workshop: Mode of Action and Introduction to PBPK Modelling

When?

Monday 17 January 2011 to Wednesday 19 January 2011

Where?

University of Surrey, Guildford

Open to:

Public, Staff, Students

Speaker:

Bette Meek, Kevin Crofton, Jennifer Seed, Doug Wolf and George Loizou

The first part of this 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 of the International Life Sciences Research Foundation (ILSI RSI/World Health Organization International Programme on Chemical Safety (WHO IPCS) for evaluating the relevance of an animal mode of action in assessing human risk and subsequent implications for dose-response analysis. 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 (including toxicogenomic) 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. 

A tutorial on a framework of the WHO IPCS will also introduce participants to the nature of data that is relevant and adequate for replacing default uncertainty factors subdivided to address kinetics and dynamics for interspecies differences and human variability with chemical specific data.  Examples will be provided and one of the mode of action case studies extended to consider adequacy of kinetic and dynamic data to replace default values for interspecies differences and human variability.

This sets the scene for an introductory course to increase knowledge and expertise in physiologically based pharmacokinetic (PBPK) modelling as a tool for improving the predictive value of chemical risk assessment, based on knowledge of mode of action.  This includes introductory presentations and ‘hands-on’ sessions, with examples of data modelling using state-of-the-art software, which has been designed to appeal to biological scientists by removing the need for extensive mathematical and programming expertise.

 Participants are 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. PBPK modeling includes hands on practical examples. The speakers/facilitators - Beet Meek, Kevin Crofton, Jennifer Seed, Doug Wolf and George Loizou - have been leaders in the development of MOA human relevance analysis and/or PBPK modeling and have extensive experience in its practical use. 

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The registration fee for participants is £850 for the 3 day course or £350 for individual days. This will include tea, coffees and a sandwich lunch. Accommodation is the responsibility of the individual to book. 

The registration deadline is 13 December. Early registration is encouraged as the course is limited to 32 participants.